rs142564545

Positions:

• chr10-79946502-C-A
• chr10-79946502-C-T

Variant summary

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

The ENST00000372292.8(SFTPD):​c.158G>T​(p.Arg53Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R53Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SFTPD ENST00000372292.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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]

(HGNC:):

ACMG classification

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	UniProt
SFTPD	NM_003019.5	c.158G>T	p.Arg53Leu	missense_variant	2/8	ENST00000372292.8	NP_003010.4
SFTPD	XM_011540087.2	c.158G>T	p.Arg53Leu	missense_variant	2/8		XP_011538389.1
SFTPD	XM_011540088.3	c.158G>T	p.Arg53Leu	missense_variant	2/7		XP_011538390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFTPD	ENST00000372292.8	c.158G>T	p.Arg53Leu	missense_variant	2/8	1	NM_003019.5	ENSP00000361366	P1
SFTPD	ENST00000444384.3	c.197G>T	p.Arg66Leu	missense_variant	2/6	3		ENSP00000394325
	ENST00000421889.1	n.334-3526C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251368 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135870

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461812 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727208

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Uncertain	0.48	D
MutationAssessor	Benign	0.63	N;.
MutationTaster	Benign	0.57	D
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0030	D;T
Sift4G	Benign	0.45	T;.
Polyphen		0.76	P;.
Vest4		0.40
MutPred		0.54		Loss of methylation at R53 (P = 0.0234);.;
MVP		0.81
MPC		0.22
ClinPred		0.66	D
GERP RS		4.6
Varity_R		0.29
gMVP		0.60

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: rs142564545; hg19: chr10-81706258;