Variant chr5-163471426-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_001142556.2(HMMR):c.613G>A(p.Glu205Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

HMMR
NM_001142556.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.46

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:

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=0.19805288).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMMR	NM_001142556.2 linkuse as main transcript	c.613G>A	p.Glu205Lys	missense_variant	7/18	ENST00000393915.9	NP_001136028.1	O75330-3
HMMR	NM_012484.3 linkuse as main transcript	c.610G>A	p.Glu204Lys	missense_variant	7/18		NP_036616.2	O75330-1
HMMR	NM_012485.3 linkuse as main transcript	c.565G>A	p.Glu189Lys	missense_variant	6/17		NP_036617.2	O75330-2
HMMR	NM_001142557.2 linkuse as main transcript	c.352G>A	p.Glu118Lys	missense_variant	4/15		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.613G>A	p.Glu205Lys	missense_variant	7/18	1	NM_001142556.2	ENSP00000377492.4		O75330-3
HMMR	ENST00000520345.5 linkuse as main transcript	c.268G>A	p.Glu90Lys	missense_variant	6/6	2		ENSP00000428481.1		E5RI30

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461708

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727152

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:

0.00000360

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2022

The c.613G>A (p.E205K) alteration is located in exon 7 (coding exon 7) of the HMMR gene. This alteration results from a G to A substitution at nucleotide position 613, causing the glutamic acid (E) at amino acid position 205 to be replaced by a lysine (K). 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

0.093

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.;.;.;.;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.94

D;T;D;D;D;D

M_CAP

Benign

0.036

MetaRNN

Benign

0.20

T;T;T;T;T;T

MetaSVM

Benign

-0.50

MutationAssessor

Uncertain

2.5

.;.;.;.;.;M

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.1

N;N;N;N;N;N

REVEL

Benign

0.059

Sift

Benign

0.067

T;D;T;T;T;T

Sift4G

Benign

0.098

T;T;T;T;T;T

Polyphen

0.91, 0.97, 0.85

.;.;P;D;P;P

Vest4

0.31, 0.29, 0.34, 0.31

MutPred

0.36

.;.;.;.;.;Gain of MoRF binding (P = 0.0064);

MVP

0.80

MPC

0.088

ClinPred

0.62

GERP RS

2.7

Varity_R

0.042

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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