Variant 10-79946525-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.42

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 made for transcript

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/exons	MANE	Protein	UniProt
SFTPD	NM_003019.5 linkuse as main transcript	c.135T>C	p.Ser45Ser	synonymous_variant	2/8	ENST00000372292.8	NP_003010.4	P35247
SFTPD	XM_011540087.2 linkuse as main transcript	c.135T>C	p.Ser45Ser	synonymous_variant	2/8		XP_011538389.1	P35247
SFTPD	XM_011540088.3 linkuse as main transcript	c.135T>C	p.Ser45Ser	synonymous_variant	2/7		XP_011538390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SFTPD	ENST00000372292.8 linkuse as main transcript	c.135T>C	p.Ser45Ser	synonymous_variant	2/8	1	NM_003019.5	ENSP00000361366.3	P35247
SFTPD	ENST00000444384.3 linkuse as main transcript	c.174T>C	p.Ser58Ser	synonymous_variant	2/6	3		ENSP00000394325.1	Q5T0M2
ENSG00000283913	ENST00000421889.1 linkuse as main transcript	n.334-3503A>G		intron_variant		3
ENSG00000283913	ENST00000453174.7 linkuse as main transcript	n.962-3503A>G		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0479

AC:

7278

AN:

151892

Hom.:

239

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0622

AC XY:

45200

AN XY:

727186

show subpopulations

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.:

AF XY:

0.0445

AC XY:

3308

AN XY:

74316

show subpopulations

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:

AN:

3478

EpiCase

AF:

0.0752

EpiControl

AF:

0.0739

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over