Variant 18-63960199-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.264A>G(p.Ile88Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,454 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: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

HMSD
NM_001123366.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.145

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:

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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=0.05004677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMSD	NM_001123366.2 link	c.264A>G	p.Ile88Met	missense_variant	Exon 4 of 4	ENST00000408945.5	NP_001116838.1	A8MTL9-1
HMSD	XM_017025710.2 link	c.264A>G	p.Ile88Met	missense_variant	Exon 4 of 5		XP_016881199.1
HMSD	XM_011525930.3 link	c.264A>G	p.Ile88Met	missense_variant	Exon 4 of 5		XP_011524232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HMSD	ENST00000408945.5 link	c.264A>G	p.Ile88Met	missense_variant	Exon 4 of 4	3	NM_001123366.2	ENSP00000386207.3	A8MTL9-1
HMSD	ENST00000526932.1 link	c.161A>G	p.Ter54Ter	splice_region_variant, stop_retained_variant	Exon 2 of 2	3		ENSP00000431632.1	P0C7T4-1
HMSD	ENST00000481726.1 link	n.236A>G		non_coding_transcript_exon_variant	Exon 3 of 6	5
HMSD	ENST00000498680.1 link	n.18A>G		non_coding_transcript_exon_variant	Exon 1 of 2	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460454

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726326

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:

0.0000584

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.264A>G (p.I88M) 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 264, causing the isoleucine (I) at amino acid position 88 to be replaced by a methionine (M). 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

0.10

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

5.9

DANN

Benign

0.063

DEOGEN2

Benign

0.10

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00064

LIST_S2

Benign

0.75

M_CAP

Benign

0.0063

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.88

MutationAssessor

Benign

-0.70

PrimateAI

Benign

0.34

PROVEAN

Benign

0.87

REVEL

Benign

0.089

Sift

Benign

0.60

Sift4G

Benign

0.45

Polyphen

0.0070

Vest4

0.041

MutPred

0.45

Gain of ubiquitination at K89 (P = 0.0818);

MVP

0.16

MPC

0.25

ClinPred

0.043

GERP RS

0.70

Varity_R

0.034

gMVP

0.054

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over