Variant 10-79940713-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003019.5(SFTPD):c.743A>G(p.Tyr248Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,970 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SFTPD
NM_003019.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SFTPD	NM_003019.5 linkuse as main transcript	c.743A>G	p.Tyr248Cys	missense_variant	7/8	ENST00000372292.8	NP_003010.4
SFTPD	XM_011540087.2 linkuse as main transcript	c.743A>G	p.Tyr248Cys	missense_variant	7/8		XP_011538389.1
SFTPD	XM_011540088.3 linkuse as main transcript	c.626A>G	p.Tyr209Cys	missense_variant	6/7		XP_011538390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SFTPD	ENST00000372292.8 linkuse as main transcript	c.743A>G	p.Tyr248Cys	missense_variant	7/8	1	NM_003019.5	ENSP00000361366	P1
SFTPD	ENST00000678361.1 linkuse as main transcript	n.2948A>G		non_coding_transcript_exon_variant	3/4
SFTPD	ENST00000679234.1 linkuse as main transcript	n.2869A>G		non_coding_transcript_exon_variant	4/5
	ENST00000421889.1 linkuse as main transcript	n.235-724T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1450970

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721796

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2023

The c.743A>G (p.Y248C) alteration is located in exon 7 (coding exon 6) of the SFTPD gene. This alteration results from a A to G substitution at nucleotide position 743, causing the tyrosine (Y) at amino acid position 248 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Uncertain

0.53

Eigen

Benign

0.013

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.69

M_CAP

Uncertain

0.088

MetaRNN

Uncertain

0.60

MetaSVM

Uncertain

0.041

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.49

Sift

Benign

0.049

Sift4G

Benign

0.080

Polyphen

1.0

Vest4

0.31

MutPred

0.70

Gain of methylation at K249 (P = 0.0123);

MVP

0.95

MPC

0.27

ClinPred

0.48

GERP RS

3.4

Varity_R

0.45

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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