Variant 5-163474063-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001142556.2(HMMR):c.911A>G(p.His304Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000249 in 1,607,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

HMMR
NM_001142556.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.571

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011004835).

BS2

High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMMR	NM_001142556.2 linkuse as main transcript	c.911A>G	p.His304Arg	missense_variant	10/18	ENST00000393915.9	NP_001136028.1	O75330-3
HMMR	NM_012484.3 linkuse as main transcript	c.908A>G	p.His303Arg	missense_variant	10/18		NP_036616.2	O75330-1
HMMR	NM_012485.3 linkuse as main transcript	c.863A>G	p.His288Arg	missense_variant	9/17		NP_036617.2	O75330-2
HMMR	NM_001142557.2 linkuse as main transcript	c.650A>G	p.His217Arg	missense_variant	7/15		NP_001136029.1	O75330-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HMMR	ENST00000393915.9 linkuse as main transcript	c.911A>G	p.His304Arg	missense_variant	10/18	1	NM_001142556.2	ENSP00000377492.4	O75330-3
HMMR	ENST00000358715.3 linkuse as main transcript	c.908A>G	p.His303Arg	missense_variant	10/18	1		ENSP00000351554.3	O75330-1
HMMR	ENST00000353866.7 linkuse as main transcript	c.863A>G	p.His288Arg	missense_variant	9/17	1		ENSP00000185942.6	O75330-2
HMMR	ENST00000432118.6 linkuse as main transcript	c.650A>G	p.His217Arg	missense_variant	7/15	2		ENSP00000402673.2	O75330-4

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000815

AC:

AN:

245344

Hom.:

AF XY:

0.0000905

AC XY:

AN XY:

132524

show subpopulations

Gnomad AFR exome

AF:

0.0000625

Gnomad AMR exome

AF:

0.0000299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000939

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000899

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1455562

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

723848

show subpopulations

Gnomad4 AFR exome

AF:

0.000211

Gnomad4 AMR exome

AF:

0.0000229

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000431

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152072

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000769

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000967

Hom.:

Bravo

AF:

0.000117

ExAC

AF:

0.0000741

AC:

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

Aug 13, 2021

The c.911A>G (p.H304R) alteration is located in exon 10 (coding exon 10) of the HMMR gene. This alteration results from a A to G substitution at nucleotide position 911, causing the histidine (H) at amino acid position 304 to be replaced by an arginine (R). 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

0.076

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.6

DANN

Benign

0.41

DEOGEN2

Benign

0.13

.;.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.68

T;T;T;T

M_CAP

Benign

0.0064

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.34

.;.;.;N

PrimateAI

Benign

0.32

PROVEAN

Benign

0.55

N;N;N;N

REVEL

Benign

0.021

Sift

Benign

0.045

D;D;D;D

Sift4G

Benign

0.27

T;T;T;T

Polyphen

0.028

B;B;B;B

Vest4

0.15

MVP

0.35

MPC

0.095

ClinPred

0.016

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.033

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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