rs6413520

Positions:

• chr10-79946525-A-C
• chr10-79946525-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003019.5(SFTPD):​c.135T>G​(p.Ser45Arg) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SFTPD NM_003019.5 missense
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21663514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFTPD	NM_003019.5	c.135T>G	p.Ser45Arg	missense_variant	2/8	ENST00000372292.8	NP_003010.4
SFTPD	XM_011540087.2	c.135T>G	p.Ser45Arg	missense_variant	2/8		XP_011538389.1
SFTPD	XM_011540088.3	c.135T>G	p.Ser45Arg	missense_variant	2/7		XP_011538390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPD	ENST00000372292.8	c.135T>G	p.Ser45Arg	missense_variant	2/8	1	NM_003019.5	ENSP00000361366.3
SFTPD	ENST00000444384.3	c.174T>G	p.Ser58Arg	missense_variant	2/6	3		ENSP00000394325.1
ENSG00000283913	ENST00000421889.1	n.334-3503A>C		intron_variant		3
ENSG00000283913	ENST00000453174.7	n.962-3503A>C		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.073	T;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	0.49	N;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.39	N;N
REVEL	Uncertain	0.37
Sift	Benign	0.25	T;T
Sift4G	Benign	0.64	T;.
Polyphen		0.26	B;.
Vest4		0.20
MutPred		0.31		Loss of glycosylation at S45 (P = 0.0159);.;
MVP		0.84
MPC		0.21
ClinPred		0.25	T
GERP RS		3.2
Varity_R		0.057
gMVP		0.33

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;