chr10-79942429-G-A

Variant names:

• chr10-79942429-G-A
• NM_003019.5:c.392C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003019.5(SFTPD):​c.392C>T​(p.Pro131Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SFTPD NM_003019.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33308387).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFTPD	NM_003019.5	c.392C>T	p.Pro131Leu	missense_variant	Exon 4 of 8	ENST00000372292.8	NP_003010.4
SFTPD	XM_011540087.2	c.392C>T	p.Pro131Leu	missense_variant	Exon 4 of 8		XP_011538389.1
SFTPD	XM_011540088.3	c.316+334C>T		intron_variant	Intron 3 of 6		XP_011538390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFTPD	ENST00000372292.8	c.392C>T	p.Pro131Leu	missense_variant	Exon 4 of 8	1	NM_003019.5	ENSP00000361366.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.392C>T (p.P131L) alteration is located in exon 4 (coding exon 3) of the SFTPD gene. This alteration results from a C to T substitution at nucleotide position 392, causing the proline (P) at amino acid position 131 to be replaced by a leucine (L). 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	Benign	0.10
BayesDel_addAF	Benign	-0.0099	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.97	L;.
PhyloP100		1.4
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Benign	0.19
Sift	Uncertain	0.015	D;D
Sift4G	Benign	0.37	T;.
Polyphen		0.99	D;.
Vest4		0.30
MutPred		0.36		Gain of MoRF binding (P = 0.0503);.;
MVP		0.74
MPC		0.28
ClinPred		0.87	D
GERP RS		5.0
Varity_R		0.17
gMVP		0.31
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr10-81702185;