dbSNP rs759290376: HMSD:p.His39Pro (chr18-63954451-A-C) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001123366.2(HMSD):c.116A>C(p.His39Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HMSD
NM_001123366.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.39

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.964

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMSD	NM_001123366.2 link	c.116A>C	p.His39Pro	missense_variant	Exon 3 of 4	ENST00000408945.5	NP_001116838.1	A8MTL9-1
HMSD	XM_017025710.2 link	c.116A>C	p.His39Pro	missense_variant	Exon 3 of 5		XP_016881199.1
HMSD	XM_011525930.3 link	c.116A>C	p.His39Pro	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.116A>C	p.His39Pro	missense_variant	Exon 3 of 4	3	NM_001123366.2	ENSP00000386207.3	A8MTL9-1
HMSD	ENST00000526932.1 link	c.13A>C	p.Ile5Leu	missense_variant	Exon 1 of 2	3		ENSP00000431632.1	P0C7T4-1
HMSD	ENST00000481726.1 link	n.88A>C		non_coding_transcript_exon_variant	Exon 2 of 6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248932

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135278

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460086

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726406

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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

Cov.:

ExAC

AF:

0.00000830

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.092

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Uncertain

0.47

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.42

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.0098

MetaRNN

Pathogenic

0.96

MetaSVM

Benign

-0.75

MutationAssessor

Pathogenic

3.4

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-9.6

REVEL

Uncertain

0.43

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

0.99

Vest4

0.61

MutPred

0.82

Loss of helix (P = 0.1299);

MVP

0.39

MPC

1.1

ClinPred

0.66

GERP RS

2.0

Varity_R

0.58

gMVP

0.47

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over