chr10-79938112-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003019.5(SFTPD):c.868T>A(p.Ser290Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0763 in 1,613,952 control chromosomes in the GnomAD database, including 6,297 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.068 ( 558 hom., cov: 32)

Exomes 𝑓: 0.077 ( 5739 hom. )

Consequence

SFTPD
NM_003019.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0550

Publications

35 publications found

Variant links:

Genes affected

SFTPD (HGNC:10803): (surfactant protein D) The protein encoded by this gene is part of the innate immune response, protecting the lungs against inhaled microorganisms and chemicals. The encoded protein may also be involved in surfactant metabolism. [provided by RefSeq, Jul 2015]

SFTPD links:

ENSG00000283913 (HGNC:):

ENSG00000283913 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020384192).

BP6

Variant 10-79938112-A-T is Benign according to our data. Variant chr10-79938112-A-T is described in ClinVar as Benign. ClinVar VariationId is 165214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003019.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFTPD	NM_003019.5	MANE Select	c.868T>A	p.Ser290Thr	missense	Exon 8 of 8	NP_003010.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SFTPD	ENST00000372292.8	TSL:1 MANE Select	c.868T>A	p.Ser290Thr	missense	Exon 8 of 8	ENSP00000361366.3
SFTPD	ENST00000678361.1		n.3073T>A		non_coding_transcript_exon	Exon 4 of 4
SFTPD	ENST00000679234.1		n.2994T>A		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.0676

AC:

10283

AN:

152102

Hom.:

551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0246

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.0783

Gnomad EAS

AF:

0.0168

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.0485

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0677

Gnomad OTH

AF:

0.0837

GnomAD2 exomes

AF:

0.0993

AC:

24963

AN:

251406

AF XY:

0.100

show subpopulations

Gnomad AFR exome

AF:

0.0223

Gnomad AMR exome

AF:

0.240

Gnomad ASJ exome

AF:

0.0748

Gnomad EAS exome

AF:

0.0142

Gnomad FIN exome

AF:

0.0559

Gnomad NFE exome

AF:

0.0680

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.0772

AC:

112884

AN:

1461732

Hom.:

5739

Cov.:

AF XY:

0.0800

AC XY:

58200

AN XY:

727144

show subpopulations

African (AFR)

AF:

0.0209

AC:

698

AN:

33476

American (AMR)

AF:

0.233

AC:

10421

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0754

AC:

1971

AN:

26136

East Asian (EAS)

AF:

0.0220

AC:

874

AN:

39698

South Asian (SAS)

AF:

0.187

AC:

16136

AN:

86258

European-Finnish (FIN)

AF:

0.0555

AC:

2964

AN:

53414

Middle Eastern (MID)

AF:

0.107

AC:

620

AN:

5768

European-Non Finnish (NFE)

AF:

0.0670

AC:

74502

AN:

1111864

Other (OTH)

AF:

0.0778

AC:

4698

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

5583

11167

16750

22334

27917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2930

5860

8790

11720

14650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0677

AC:

10310

AN:

152220

Hom.:

558

Cov.:

AF XY:

0.0713

AC XY:

5306

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0247

AC:

1026

AN:

41550

American (AMR)

AF:

0.172

AC:

2623

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0783

AC:

272

AN:

3472

East Asian (EAS)

AF:

0.0168

AC:

AN:

5172

South Asian (SAS)

AF:

0.201

AC:

969

AN:

4824

European-Finnish (FIN)

AF:

0.0485

AC:

514

AN:

10598

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0677

AC:

4604

AN:

68000

Other (OTH)

AF:

0.0876

AC:

185

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

491

981

1472

1962

2453

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0690

Hom.:

318

Bravo

AF:

0.0730

TwinsUK

AF:

0.0647

AC:

240

ALSPAC

AF:

0.0654

AC:

252

ESP6500AA

AF:

0.0218

AC:

ESP6500EA

AF:

0.0733

AC:

630

ExAC

AF:

0.0942

AC:

11436

Asia WGS

AF:

0.126

AC:

437

AN:

3478

EpiCase

AF:

0.0713

EpiControl

AF:

0.0668

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ser290Thr in exon 8 of SFTPD: This variant is not expected to have clinical sign ificance because it has been identified in 7.3% (630/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs3088308).

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.051

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

-0.055

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.1

REVEL

Benign

0.050

Sift

Benign

0.32

Sift4G

Benign

0.32

Polyphen

0.016

Vest4

0.039

MPC

0.29

ClinPred

0.0030

GERP RS

3.2

Varity_R

0.28

gMVP

0.40

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over