Variant 18-63954463-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001123366.2(HMSD):c.128A>T(p.Gln43Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,128 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HMSD
NM_001123366.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.41

Variant links:

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]

HMSD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 link	c.128A>T	p.Gln43Leu	missense_variant	Exon 3 of 4	ENST00000408945.5	NP_001116838.1	A8MTL9-1
HMSD	XM_017025710.2 link	c.128A>T	p.Gln43Leu	missense_variant	Exon 3 of 5		XP_016881199.1
HMSD	XM_011525930.3 link	c.128A>T	p.Gln43Leu	missense_variant	Exon 3 of 5		XP_011524232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HMSD	ENST00000408945.5 link	c.128A>T	p.Gln43Leu	missense_variant	Exon 3 of 4	3	NM_001123366.2	ENSP00000386207.3	A8MTL9-1
HMSD	ENST00000526932.1 link	c.25A>T	p.Ser9Cys	missense_variant	Exon 1 of 2	3		ENSP00000431632.1	P0C7T4-1
HMSD	ENST00000481726.1 link	n.100A>T		non_coding_transcript_exon_variant	Exon 2 of 6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

249030

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135332

show subpopulations

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:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461128

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726910

show subpopulations

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.128A>T (p.Q43L) alteration is located in exon 3 (coding exon 2) of the HMSD gene. This alteration results from a A to T substitution at nucleotide position 128, causing the glutamine (Q) at amino acid position 43 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

0.29

BayesDel_addAF

Uncertain

0.077

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

Eigen

Benign

-0.090

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.57

MetaSVM

Benign

-0.82

MutationAssessor

Pathogenic

3.1

PrimateAI

Benign

0.31

PROVEAN

Pathogenic

-6.2

REVEL

Uncertain

0.38

Sift

Benign

0.048

Sift4G

Benign

0.071

Polyphen

0.83

Vest4

0.40

MutPred

0.52

Gain of catalytic residue at S44 (P = 0.0565);

MVP

0.63

MPC

0.61

ClinPred

0.94

GERP RS

3.2

Varity_R

0.29

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over