Variant 18-63954442-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001123366.2(HMSD):c.107G>A(p.Gly36Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 151,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HMSD
NM_001123366.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.461

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.092339665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HMSD	NM_001123366.2 linkuse as main transcript	c.107G>A	p.Gly36Glu	missense_variant	3/4	ENST00000408945.5
HMSD	XM_017025710.2 linkuse as main transcript	c.107G>A	p.Gly36Glu	missense_variant	3/5
HMSD	XM_011525930.3 linkuse as main transcript	c.107G>A	p.Gly36Glu	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMSD	ENST00000408945.5 linkuse as main transcript	c.107G>A	p.Gly36Glu	missense_variant	3/4	3	NM_001123366.2	P1	A8MTL9-1
HMSD	ENST00000526932.1 linkuse as main transcript	c.4G>A	p.Glu2Lys	missense_variant	1/2	3			P0C7T4-1
HMSD	ENST00000481726.1 linkuse as main transcript	n.79G>A		non_coding_transcript_exon_variant	2/6	5

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

151128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000989

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1459534

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726130

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:

0.00

GnomAD4 genome

AF:

0.0000265

AC:

AN:

151128

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

73850

show subpopulations

Gnomad4 AFR

AF:

0.0000989

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000113

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

Dec 27, 2022

The c.107G>A (p.G36E) alteration is located in exon 3 (coding exon 2) of the HMSD gene. This alteration results from a G to A substitution at nucleotide position 107, causing the glycine (G) at amino acid position 36 to be replaced by a glutamic acid (E). 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

0.14

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.56

Cadd

Benign

0.13

Dann

Benign

0.44

DEOGEN2

Benign

0.068

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0049

M_CAP

Benign

0.0034

MetaRNN

Benign

0.092

MetaSVM

Benign

-0.87

MutationTaster

Benign

1.0

N;N

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.11

Vest4

0.12

MutPred

0.25

Gain of ubiquitination at E2 (P = 0.0177);

MVP

0.014

ClinPred

0.060

GERP RS

-4.9

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