Genetic Variant HMMR:p.Ala485Val (chr5-163482710-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001142556.2(HMMR):c.1454C>T(p.Ala485Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,609,806 control chromosomes in the GnomAD database, including 46,728 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 4957 hom., cov: 32)

Exomes 𝑓: 0.23 ( 41771 hom. )

Consequence

HMMR
NM_001142556.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.30

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-AS1 (HGNC:49149): (HMMR antisense RNA 1)

HMMR-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045486987).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMMR	NM_001142556.2 link	c.1454C>T	p.Ala485Val	missense_variant	Exon 13 of 18	ENST00000393915.9	NP_001136028.1	O75330-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HMMR	ENST00000393915.9 link	c.1454C>T	p.Ala485Val	missense_variant	Exon 13 of 18	1	NM_001142556.2	ENSP00000377492.4	O75330-3
HMMR	ENST00000358715.3 link	c.1451C>T	p.Ala484Val	missense_variant	Exon 13 of 18	1		ENSP00000351554.3	O75330-1
HMMR	ENST00000353866.7 link	c.1406C>T	p.Ala469Val	missense_variant	Exon 12 of 17	1		ENSP00000185942.6	O75330-2
HMMR	ENST00000432118.6 link	c.1193C>T	p.Ala398Val	missense_variant	Exon 10 of 15	2		ENSP00000402673.2	O75330-4

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37924

AN:

151684

Hom.:

4953

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.208

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.0621

Gnomad SAS

AF:

0.258

Gnomad FIN

AF:

0.283

Gnomad MID

AF:

0.268

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.232

GnomAD3 exomes

AF:

0.226

AC:

56686

AN:

251072

Hom.:

7063

AF XY:

0.231

AC XY:

31300

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.289

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.216

Gnomad EAS exome

AF:

0.0664

Gnomad SAS exome

AF:

0.258

Gnomad FIN exome

AF:

0.282

Gnomad NFE exome

AF:

0.243

Gnomad OTH exome

AF:

0.235

GnomAD4 exome

AF:

0.234

AC:

341599

AN:

1458004

Hom.:

41771

Cov.:

AF XY:

0.235

AC XY:

170653

AN XY:

725436

show subpopulations

Gnomad4 AFR exome

AF:

0.294

Gnomad4 AMR exome

AF:

0.164

Gnomad4 ASJ exome

AF:

0.218

Gnomad4 EAS exome

AF:

0.0554

Gnomad4 SAS exome

AF:

0.262

Gnomad4 FIN exome

AF:

0.281

Gnomad4 NFE exome

AF:

0.238

Gnomad4 OTH exome

AF:

0.233

GnomAD4 genome

AF:

0.250

AC:

37935

AN:

151802

Hom.:

4957

Cov.:

AF XY:

0.249

AC XY:

18427

AN XY:

74142

show subpopulations

Gnomad4 AFR

AF:

0.297

Gnomad4 AMR

AF:

0.207

Gnomad4 ASJ

AF:

0.223

Gnomad4 EAS

AF:

0.0620

Gnomad4 SAS

AF:

0.258

Gnomad4 FIN

AF:

0.283

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.238

Alfa

AF:

0.236

Hom.:

8747

Bravo

AF:

0.241

TwinsUK

AF:

0.236

AC:

875

ALSPAC

AF:

0.235

AC:

904

ESP6500AA

AF:

0.290

AC:

1278

ESP6500EA

AF:

0.238

AC:

2046

ExAC

AF:

0.233

AC:

28232

Asia WGS

AF:

0.184

AC:

641

AN:

3478

EpiCase

AF:

0.243

EpiControl

AF:

0.237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.53

DEOGEN2

Benign

0.21

.;.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.043

T;T;T;T

MetaRNN

Benign

0.0045

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.5

.;.;.;N

PrimateAI

Benign

0.32

PROVEAN

Benign

1.7

N;N;N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.80

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.018

MPC

0.059

ClinPred

0.0031

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.017

gMVP

0.040

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