chr18-63960243-G-T

Variant names:

• chr18-63960243-G-T
• rs755306977
• NM_001123366.2:c.308G>T

Variant summary

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

The NM_001123366.2(HMSD):​c.308G>T​(p.Arg103Leu) 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. 15/21 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: HMSD NM_001123366.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.874

Genes affected

HMSD (HGNC:23037): (histocompatibility minor serpin domain containing) This gene encodes a serpin-domain containing protein that may function as a serine protease inhibitor. This gene is primarily expressed in cells of myeloid lineage. A polymorphism in this gene may result in the expression a splice variant that encodes a minor histocompatibility antigen. [provided by RefSeq, Oct 2010]

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=0.13675383).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMSD	NM_001123366.2	c.308G>T	p.Arg103Leu	missense_variant	Exon 4 of 4	ENST00000408945.5	NP_001116838.1
HMSD	XM_017025710.2	c.308G>T	p.Arg103Leu	missense_variant	Exon 4 of 5		XP_016881199.1
HMSD	XM_011525930.3	c.308G>T	p.Arg103Leu	missense_variant	Exon 4 of 5		XP_011524232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMSD	ENST00000408945.5	c.308G>T	p.Arg103Leu	missense_variant	Exon 4 of 4	3	NM_001123366.2	ENSP00000386207.3
HMSD	ENST00000481726.1	n.280G>T		non_coding_transcript_exon_variant	Exon 3 of 6	5
HMSD	ENST00000498680.1	n.62G>T		non_coding_transcript_exon_variant	Exon 1 of 2	5
HMSD	ENST00000526932.1	c.*43G>T		downstream_gene_variant		3		ENSP00000431632.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	9.6
DANN	Benign	0.95
DEOGEN2	Benign	0.34	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0075	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	-0.26	N
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.21
Sift	Benign	0.092	T
Sift4G	Benign	0.074	T
Polyphen		0.46	P
Vest4		0.12
MutPred		0.45		Loss of disorder (P = 0.0384);
MVP		0.16
MPC		0.33
ClinPred		0.31	T
GERP RS		0.41
Varity_R		0.068
gMVP		0.12

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: rs755306977; hg19: chr18-61627477; COSMIC: COSV99065247; COSMIC: COSV99065247;