rs721917

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003019.5(SFTPD):c.92T>C(p.Met31Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,613,692 control chromosomes in the GnomAD database, including 159,571 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.43 ( 14337 hom., cov: 33)

Exomes 𝑓: 0.44 ( 145234 hom. )

Consequence

SFTPD
NM_003019.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.186

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.5746423E-6).

BP6

Variant 10-79946568-A-G is Benign according to our data. Variant chr10-79946568-A-G is described in ClinVar as [Benign]. Clinvar id is 165219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPD	NM_003019.5 link	c.92T>C	p.Met31Thr	missense_variant	Exon 2 of 8	ENST00000372292.8	NP_003010.4	P35247
SFTPD	XM_011540087.2 link	c.92T>C	p.Met31Thr	missense_variant	Exon 2 of 8		XP_011538389.1	P35247
SFTPD	XM_011540088.3 link	c.92T>C	p.Met31Thr	missense_variant	Exon 2 of 7		XP_011538390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SFTPD	ENST00000372292.8 link	c.92T>C	p.Met31Thr	missense_variant	Exon 2 of 8	1	NM_003019.5	ENSP00000361366.3	P35247
SFTPD	ENST00000444384.3 link	c.131T>C	p.Met44Thr	missense_variant	Exon 2 of 6	3		ENSP00000394325.1	Q5T0M2
ENSG00000283913	ENST00000421889.1 link	n.334-3460A>G		intron_variant	Intron 3 of 3	3
ENSG00000283913	ENST00000453174.7 link	n.962-3460A>G		intron_variant	Intron 7 of 7	2

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

65259

AN:

152002

Hom.:

14309

Cov.:

show subpopulations

Gnomad AFR

AF:

0.404

Gnomad AMI

AF:

0.315

Gnomad AMR

AF:

0.414

Gnomad ASJ

AF:

0.408

Gnomad EAS

AF:

0.611

Gnomad SAS

AF:

0.688

Gnomad FIN

AF:

0.389

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.426

Gnomad OTH

AF:

0.407

GnomAD3 exomes

AF:

0.466

AC:

117072

AN:

251222

Hom.:

28639

AF XY:

0.476

AC XY:

64660

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.408

Gnomad AMR exome

AF:

0.442

Gnomad ASJ exome

AF:

0.400

Gnomad EAS exome

AF:

0.630

Gnomad SAS exome

AF:

0.673

Gnomad FIN exome

AF:

0.388

Gnomad NFE exome

AF:

0.421

Gnomad OTH exome

AF:

0.440

GnomAD4 exome

AF:

0.440

AC:

643401

AN:

1461572

Hom.:

145234

Cov.:

AF XY:

0.447

AC XY:

325140

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.400

Gnomad4 AMR exome

AF:

0.440

Gnomad4 ASJ exome

AF:

0.404

Gnomad4 EAS exome

AF:

0.603

Gnomad4 SAS exome

AF:

0.674

Gnomad4 FIN exome

AF:

0.393

Gnomad4 NFE exome

AF:

0.421

Gnomad4 OTH exome

AF:

0.440

GnomAD4 genome

AF:

0.430

AC:

65341

AN:

152120

Hom.:

14337

Cov.:

AF XY:

0.433

AC XY:

32206

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.405

Gnomad4 AMR

AF:

0.414

Gnomad4 ASJ

AF:

0.408

Gnomad4 EAS

AF:

0.611

Gnomad4 SAS

AF:

0.688

Gnomad4 FIN

AF:

0.389

Gnomad4 NFE

AF:

0.426

Gnomad4 OTH

AF:

0.413

Alfa

AF:

0.423

Hom.:

35660

Bravo

AF:

0.425

TwinsUK

AF:

0.412

AC:

1526

ALSPAC

AF:

0.431

AC:

1660

ESP6500AA

AF:

0.401

AC:

1769

ESP6500EA

AF:

0.420

AC:

3610

ExAC

AF:

0.469

AC:

56954

Asia WGS

AF:

0.632

AC:

2196

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 21310059, 22509983, 21934714, 22289856, 24111992, 15661913, 23577114, 12032263, 30013576) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Aug 06, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Met31Thr in exon 02 of SFTPD: This variant is not expected to have clinical si gnificance because it has been identified in 67% (11088/16508) of South Asian ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org; dbSNP rs721917). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.27

CADD

Benign

0.24

DANN

Benign

0.34

DEOGEN2

Benign

0.075

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.074

T;T

MetaRNN

Benign

0.0000056

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.16

N;N

REVEL

Uncertain

0.37

Sift

Benign

0.34

T;T

Sift4G

Benign

0.46

T;.

Polyphen

0.0

B;.

Vest4

0.024

MPC

0.20

ClinPred

0.0080

GERP RS

-1.4

Varity_R

0.041

gMVP

0.41

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