Variant 5-163464753-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_001142556.2(HMMR):c.176A>T(p.Asp59Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,658 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

HMMR
NM_001142556.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.26

Variant links:

Genes affected

HMMR (HGNC:5012): (hyaluronan mediated motility receptor) The protein encoded by this gene is involved in cell motility. It is expressed in breast tissue and together with other proteins, it forms a complex with BRCA1 and BRCA2, thus is potentially associated with higher risk of breast cancer. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Dec 2008]

HMMR links:

HMMR (HGNC:):

HMMR links:

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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/exons	MANE	Protein	UniProt
HMMR	NM_001142556.2 linkuse as main transcript	c.176A>T	p.Asp59Val	missense_variant	3/18	ENST00000393915.9	NP_001136028.1	O75330-3
HMMR	NM_012484.3 linkuse as main transcript	c.176A>T	p.Asp59Val	missense_variant	3/18		NP_036616.2	O75330-1
HMMR	NM_012485.3 linkuse as main transcript	c.176A>T	p.Asp59Val	missense_variant	3/17		NP_036617.2	O75330-2
HMMR	NM_001142557.2 linkuse as main transcript	c.12+4015A>T		intron_variant			NP_001136029.1	O75330-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMMR	ENST00000393915.9 linkuse as main transcript	c.176A>T	p.Asp59Val	missense_variant	3/18	1	NM_001142556.2	ENSP00000377492.4		O75330-3
HMMR	ENST00000520345 linkuse as main transcript	c.-122A>T		5_prime_UTR_variant	3/6	2		ENSP00000428481.1		E5RI30

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460658

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726700

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 14, 2023

The c.176A>T (p.D59V) alteration is located in exon 3 (coding exon 3) of the HMMR gene. This alteration results from a A to T substitution at nucleotide position 176, causing the aspartic acid (D) at amino acid position 59 to be replaced by a valine (V). 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

-0.078

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

.;.;T

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;M;M

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.9

D;N;N

REVEL

Benign

0.18

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

0.96

D;P;D

Vest4

0.51

MutPred

0.19

Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);

MVP

0.75

MPC

0.43

ClinPred

0.96

GERP RS

5.2

Varity_R

0.20

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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