rs375545599

Variant names:

• chr18-63954466-C-A
• NM_001123366.2:c.131C>A

Your query was ambiguous. Multiple possible variants found:

• chr18-63954466-C-A
• chr18-63954466-C-T

Variant summary

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

The NM_001123366.2(HMSD):​c.131C>A​(p.Ser44*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HMSD NM_001123366.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMSD	NM_001123366.2	c.131C>A	p.Ser44*	stop_gained	Exon 3 of 4	ENST00000408945.5	NP_001116838.1
HMSD	XM_017025710.2	c.131C>A	p.Ser44*	stop_gained	Exon 3 of 5		XP_016881199.1
HMSD	XM_011525930.3	c.131C>A	p.Ser44*	stop_gained	Exon 3 of 5		XP_011524232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMSD	ENST00000408945.5	c.131C>A	p.Ser44*	stop_gained	Exon 3 of 4	3	NM_001123366.2	ENSP00000386207.3
HMSD	ENST00000526932.1	c.28C>A	p.His10Asn	missense_variant	Exon 1 of 2	3		ENSP00000431632.1
HMSD	ENST00000481726.1	n.103C>A		non_coding_transcript_exon_variant	Exon 2 of 6	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461014 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726836

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	28
DANN	Benign	0.97
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.0060	N
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.98	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Benign	0.053
Vest4		0.30
MutPred		0.24		Gain of relative solvent accessibility (P = 0.0999);
MVP		0.055
ClinPred		0.86	D
GERP RS		-0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-61621700;