rs299284

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000520345(HMMR):​c.-69C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.105 in 1,605,700 control chromosomes in the GnomAD database, including 9,376 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.10 ( 852 hom., cov: 32)
Exomes 𝑓: 0.11 ( 8524 hom. )

Consequence

HMMR
ENST00000520345 5_prime_UTR_premature_start_codon_gain

Scores

5
6
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.93
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HMMRNM_001142556.2 linkuse as main transcriptc.277C>T p.Arg93Cys missense_variant 5/18 ENST00000393915.9 NP_001136028.1 O75330-3
HMMRNM_012484.3 linkuse as main transcriptc.274C>T p.Arg92Cys missense_variant 5/18 NP_036616.2 O75330-1
HMMRNM_012485.3 linkuse as main transcriptc.229C>T p.Arg77Cys missense_variant 4/17 NP_036617.2 O75330-2
HMMRNM_001142557.2 linkuse as main transcriptc.16C>T p.Arg6Cys missense_variant 2/15 NP_001136029.1 O75330-4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HMMRENST00000520345 linkuse as main transcriptc.-69C>T 5_prime_UTR_premature_start_codon_gain_variant 4/62 ENSP00000428481.1 E5RI30
HMMRENST00000393915.9 linkuse as main transcriptc.277C>T p.Arg93Cys missense_variant 5/181 NM_001142556.2 ENSP00000377492.4 O75330-3
HMMRENST00000520345 linkuse as main transcriptc.-69C>T 5_prime_UTR_variant 4/62 ENSP00000428481.1 E5RI30

Frequencies

GnomAD3 genomes
AF:
0.103
AC:
15590
AN:
152000
Hom.:
855
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0914
Gnomad AMI
AF:
0.158
Gnomad AMR
AF:
0.0826
Gnomad ASJ
AF:
0.107
Gnomad EAS
AF:
0.0127
Gnomad SAS
AF:
0.101
Gnomad FIN
AF:
0.113
Gnomad MID
AF:
0.133
Gnomad NFE
AF:
0.118
Gnomad OTH
AF:
0.0967
GnomAD3 exomes
AF:
0.0992
AC:
24368
AN:
245592
Hom.:
1404
AF XY:
0.102
AC XY:
13576
AN XY:
132980
show subpopulations
Gnomad AFR exome
AF:
0.0904
Gnomad AMR exome
AF:
0.0590
Gnomad ASJ exome
AF:
0.0981
Gnomad EAS exome
AF:
0.00810
Gnomad SAS exome
AF:
0.101
Gnomad FIN exome
AF:
0.123
Gnomad NFE exome
AF:
0.121
Gnomad OTH exome
AF:
0.117
GnomAD4 exome
AF:
0.106
AC:
153415
AN:
1453582
Hom.:
8524
Cov.:
30
AF XY:
0.106
AC XY:
76730
AN XY:
723380
show subpopulations
Gnomad4 AFR exome
AF:
0.0927
Gnomad4 AMR exome
AF:
0.0608
Gnomad4 ASJ exome
AF:
0.0980
Gnomad4 EAS exome
AF:
0.0156
Gnomad4 SAS exome
AF:
0.102
Gnomad4 FIN exome
AF:
0.126
Gnomad4 NFE exome
AF:
0.110
Gnomad4 OTH exome
AF:
0.103
GnomAD4 genome
AF:
0.102
AC:
15588
AN:
152118
Hom.:
852
Cov.:
32
AF XY:
0.103
AC XY:
7647
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.0911
Gnomad4 AMR
AF:
0.0824
Gnomad4 ASJ
AF:
0.107
Gnomad4 EAS
AF:
0.0128
Gnomad4 SAS
AF:
0.100
Gnomad4 FIN
AF:
0.113
Gnomad4 NFE
AF:
0.118
Gnomad4 OTH
AF:
0.0981
Alfa
AF:
0.112
Hom.:
2499
Bravo
AF:
0.0978
TwinsUK
AF:
0.105
AC:
390
ALSPAC
AF:
0.109
AC:
421
ESP6500AA
AF:
0.0887
AC:
391
ESP6500EA
AF:
0.118
AC:
1012
ExAC
AF:
0.104
AC:
12593
Asia WGS
AF:
0.0650
AC:
227
AN:
3478
EpiCase
AF:
0.121
EpiControl
AF:
0.118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.090
CADD
Pathogenic
34
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.44
.;.;.;T
Eigen
Pathogenic
0.72
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.74
T;D;D;D
MetaRNN
Benign
0.0026
T;T;T;T
MetaSVM
Benign
-0.88
T
MutationAssessor
Uncertain
2.7
.;.;.;M
PrimateAI
Uncertain
0.55
T
PROVEAN
Pathogenic
-5.4
D;D;D;D
REVEL
Uncertain
0.30
Sift
Uncertain
0.0090
D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.75
MPC
0.42
ClinPred
0.016
T
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.54
gMVP
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.41
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.41
Position offset: 15

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.

Other links and lift over

dbSNP: rs299284; hg19: chr5-162896650; COSMIC: COSV62374209; COSMIC: COSV62374209; API