Genetic Variant SFTPD:p.Thr275Thr (chr10-79938155-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_003019.5(SFTPD):c.825G>A(p.Thr275Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000746 in 1,610,670 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00039 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00078 ( 19 hom. )

Consequence

SFTPD
NM_003019.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.80

Publications

0 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 10-79938155-C-T is Benign according to our data. Variant chr10-79938155-C-T is described in ClinVar as [Benign]. Clinvar id is 3049291.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.8 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPD	NM_003019.5 link	c.825G>A	p.Thr275Thr	synonymous_variant	Exon 8 of 8	ENST00000372292.8	NP_003010.4	P35247
SFTPD	XM_011540087.2 link	c.825G>A	p.Thr275Thr	synonymous_variant	Exon 8 of 8		XP_011538389.1	P35247
SFTPD	XM_011540088.3 link	c.708G>A	p.Thr236Thr	synonymous_variant	Exon 7 of 7		XP_011538390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPD	ENST00000372292.8 link	c.825G>A	p.Thr275Thr	synonymous_variant	Exon 8 of 8	1	NM_003019.5	ENSP00000361366.3		P35247

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00156

AC:

392

AN:

251248

AF XY:

0.00208

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.000783

AC:

1142

AN:

1458390

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

806

AN XY:

724648

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33426

American (AMR)

AF:

0.00

AC:

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39570

South Asian (SAS)

AF:

0.0126

AC:

1086

AN:

86196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000902

AC:

AN:

1109070

Other (OTH)

AF:

0.000714

AC:

AN:

60206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

130

196

261

326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000387

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41562

American (AMR)

AF:

0.0000654

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.0112

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000227

Hom.:

Bravo

AF:

0.000113

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SFTPD-related disorder

Benign:1

Dec 19, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.63

PhyloP100

-2.8

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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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10-79938155-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over