Variant chr18-63960194-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001123366.2(HMSD):c.259A>G(p.Thr87Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,612,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

HMSD
NM_001123366.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.919

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:

HMSD (HGNC:):

HMSD links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056586117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMSD	NM_001123366.2 linkuse as main transcript	c.259A>G	p.Thr87Ala	missense_variant	4/4	ENST00000408945.5	NP_001116838.1	A8MTL9-1
HMSD	XM_017025710.2 linkuse as main transcript	c.259A>G	p.Thr87Ala	missense_variant	4/5		XP_016881199.1
HMSD	XM_011525930.3 linkuse as main transcript	c.259A>G	p.Thr87Ala	missense_variant	4/5		XP_011524232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HMSD	ENST00000408945.5 linkuse as main transcript	c.259A>G	p.Thr87Ala	missense_variant	4/4	3	NM_001123366.2	ENSP00000386207.3	A8MTL9-1
HMSD	ENST00000526932.1 linkuse as main transcript	c.156A>G	p.Gln52Gln	synonymous_variant	2/2	3		ENSP00000431632.1	P0C7T4-1
HMSD	ENST00000481726.1 linkuse as main transcript	n.231A>G		non_coding_transcript_exon_variant	3/6	5
HMSD	ENST00000498680.1 linkuse as main transcript	n.13A>G		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460346

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726266

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2024

The c.259A>G (p.T87A) alteration is located in exon 4 (coding exon 3) of the HMSD gene. This alteration results from a A to G substitution at nucleotide position 259, causing the threonine (T) at amino acid position 87 to be replaced by an alanine (A). 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

0.087

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.096

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.57

M_CAP

Benign

0.0061

MetaRNN

Benign

0.057

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.71

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.13

REVEL

Benign

0.095

Sift

Uncertain

0.023

Sift4G

Uncertain

0.054

Polyphen

0.0040

Vest4

0.024

MutPred

0.42

Loss of methylation at K82 (P = 0.1043);

MVP

0.11

MPC

0.23

ClinPred

0.048

GERP RS

-0.48

Varity_R

0.024

gMVP

0.028

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

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