10-79938112-A-T

Position:

• chr10-79938112-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.068 (558 hom., cov: 32)
  • Exomes 𝑓: 0.077 (5739 hom.)
• Consequence: SFTPD NM_003019.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0550

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPD	NM_003019.5	c.868T>A	p.Ser290Thr	missense_variant	8/8	ENST00000372292.8	NP_003010.4
SFTPD	XM_011540087.2	c.868T>A	p.Ser290Thr	missense_variant	8/8		XP_011538389.1
SFTPD	XM_011540088.3	c.751T>A	p.Ser251Thr	missense_variant	7/7		XP_011538390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPD	ENST00000372292.8	c.868T>A	p.Ser290Thr	missense_variant	8/8	1	NM_003019.5	ENSP00000361366	P1
SFTPD	ENST00000678361.1	n.3073T>A		non_coding_transcript_exon_variant	4/4
SFTPD	ENST00000679234.1	n.2994T>A		non_coding_transcript_exon_variant	5/5
	ENST00000421889.1	n.234+1456A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0676 AC: 10283 AN: 152102 Hom.: 551 Cov.: 32

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

GnomAD3 exomes AF: 0.0993 AC: 24963 AN: 251406 Hom.: 2017 AF XY: 0.100 AC XY: 13584 AN XY: 135876

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 SAS exome AF: 0.187

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.: 33 AF XY: 0.0800 AC XY: 58200 AN XY: 727144

Gnomad4 AFR exome AF: 0.0209

Gnomad4 AMR exome AF: 0.233

Gnomad4 ASJ exome AF: 0.0754

Gnomad4 EAS exome AF: 0.0220

Gnomad4 SAS exome AF: 0.187

Gnomad4 FIN exome AF: 0.0555

Gnomad4 NFE exome AF: 0.0670

Gnomad4 OTH exome AF: 0.0778

GnomAD4 genome AF: 0.0677 AC: 10310 AN: 152220 Hom.: 558 Cov.: 32 AF XY: 0.0713 AC XY: 5306 AN XY: 74414

Gnomad4 AFR AF: 0.0247

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.0783

Gnomad4 EAS AF: 0.0168

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.0485

Gnomad4 NFE AF: 0.0677

Gnomad4 OTH AF: 0.0876

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: 96

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

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Benign	0.74
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	0.98	P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.050
Sift	Benign	0.32	T
Sift4G	Benign	0.32	T
Polyphen		0.016	B
Vest4		0.039
MPC		0.29
ClinPred		0.0030	T
GERP RS		3.2
Varity_R		0.28
gMVP		0.40

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

LitVar

Other links and lift over

dbSNP: rs3088308; hg19: chr10-81697868; COSMIC: COSV64852764; COSMIC: COSV64852764;