10-79946525-A-G

Variant names:

• chr10-79946525-A-G
• rs6413520
• NM_003019.5:c.135T>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003019.5(SFTPD):​c.135T>C​(p.Ser45Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 1,613,760 control chromosomes in the GnomAD database, including 3,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.048 (239 hom., cov: 33)
  • Exomes 𝑓: 0.063 (3282 hom.)
• Consequence: SFTPD NM_003019.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.42

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]

ENSG00000283913 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 10-79946525-A-G is Benign according to our data. Variant chr10-79946525-A-G is described in ClinVar as [Benign]. Clinvar id is 165218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.42 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPD	NM_003019.5	c.135T>C	p.Ser45Ser	synonymous_variant	Exon 2 of 8	ENST00000372292.8	NP_003010.4
SFTPD	XM_011540087.2	c.135T>C	p.Ser45Ser	synonymous_variant	Exon 2 of 8		XP_011538389.1
SFTPD	XM_011540088.3	c.135T>C	p.Ser45Ser	synonymous_variant	Exon 2 of 7		XP_011538390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPD	ENST00000372292.8	c.135T>C	p.Ser45Ser	synonymous_variant	Exon 2 of 8	1	NM_003019.5	ENSP00000361366.3
SFTPD	ENST00000444384.3	c.174T>C	p.Ser58Ser	synonymous_variant	Exon 2 of 6	3		ENSP00000394325.1
ENSG00000283913	ENST00000421889.1	n.334-3503A>G		intron_variant	Intron 3 of 3	3
ENSG00000283913	ENST00000453174.7	n.962-3503A>G		intron_variant	Intron 7 of 7	2

Frequencies

GnomAD3 genomes AF: 0.0479 AC: 7278 AN: 151892 Hom.: 239 Cov.: 33

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0480

Gnomad ASJ AF: 0.0721

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00852

Gnomad FIN AF: 0.0352

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0750

Gnomad OTH AF: 0.0541

GnomAD3 exomes AF: 0.0462 AC: 11604 AN: 251372 Hom.: 381 AF XY: 0.0458 AC XY: 6222 AN XY: 135872

Gnomad AFR exome AF: 0.0128

Gnomad AMR exome AF: 0.0332

Gnomad ASJ exome AF: 0.0623

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.00852

Gnomad FIN exome AF: 0.0401

Gnomad NFE exome AF: 0.0717

Gnomad OTH exome AF: 0.0543

GnomAD4 exome AF: 0.0634 AC: 92658 AN: 1461750 Hom.: 3282 Cov.: 32 AF XY: 0.0622 AC XY: 45200 AN XY: 727186

Gnomad4 AFR exome AF: 0.0107

Gnomad4 AMR exome AF: 0.0348

Gnomad4 ASJ exome AF: 0.0604

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00892

Gnomad4 FIN exome AF: 0.0405

Gnomad4 NFE exome AF: 0.0743

Gnomad4 OTH exome AF: 0.0562

GnomAD4 genome AF: 0.0479 AC: 7274 AN: 152010 Hom.: 239 Cov.: 33 AF XY: 0.0445 AC XY: 3308 AN XY: 74316

Gnomad4 AFR AF: 0.0135

Gnomad4 AMR AF: 0.0479

Gnomad4 ASJ AF: 0.0721

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00852

Gnomad4 FIN AF: 0.0352

Gnomad4 NFE AF: 0.0750

Gnomad4 OTH AF: 0.0540

Alfa AF: 0.0677 Hom.: 478

Bravo AF: 0.0475

Asia WGS AF: 0.00924 AC: 32 AN: 3478

EpiCase AF: 0.0752

EpiControl AF: 0.0739

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

Ser45Ser in exon 2 of SFTPD: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 6.8% (589/8600) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs6413520). -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.6
DANN	Benign	0.69

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: rs6413520; hg19: chr10-81706281; COSMIC: COSV64852944;