Variant 5-163473558-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001142556.2(HMMR):c.904+1G>T variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.0000065 in 1,539,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

HMMR
NM_001142556.2 splice_donor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.70

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 Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
HMMR	NM_001142556.2 linkuse as main transcript	c.904+1G>T	splice_donor_variant, intron_variant	ENST00000393915.9	NP_001136028.1	O75330-3
HMMR	NM_012484.3 linkuse as main transcript	c.901+1G>T	splice_donor_variant, intron_variant		NP_036616.2	O75330-1
HMMR	NM_012485.3 linkuse as main transcript	c.856+1G>T	splice_donor_variant, intron_variant		NP_036617.2	O75330-2
HMMR	NM_001142557.2 linkuse as main transcript	c.643+1G>T	splice_donor_variant, intron_variant		NP_001136029.1	O75330-4

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
HMMR	ENST00000393915.9 linkuse as main transcript	c.904+1G>T	splice_donor_variant, intron_variant	1	NM_001142556.2	ENSP00000377492.4	O75330-3
HMMR	ENST00000358715.3 linkuse as main transcript	c.901+1G>T	splice_donor_variant, intron_variant	1		ENSP00000351554.3	O75330-1
HMMR	ENST00000353866.7 linkuse as main transcript	c.856+1G>T	splice_donor_variant, intron_variant	1		ENSP00000185942.6	O75330-2
HMMR	ENST00000432118.6 linkuse as main transcript	c.643+1G>T	splice_donor_variant, intron_variant	2		ENSP00000402673.2	O75330-4

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000649

AC:

AN:

1387512

Hom.:

Cov.:

AF XY:

0.00000724

AC XY:

AN XY:

690914

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:

0.00000845

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151908

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial cancer of breast

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Mar 20, 2019

This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PVS1,PM2. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Uncertain

0.96

GERP RS

3.8

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.95

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.99

Position offset: -1

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