5-163464744-T-A

Position:

• chr5-163464744-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The ENST00000520345(HMMR):​c.-131T>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HMMR ENST00000520345 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.459

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08175853).
• BP6: Variant 5-163464744-T-A is Benign according to our data. Variant chr5-163464744-T-A is described in ClinVar as [Benign]. Clinvar id is 2445307.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMMR	NM_001142556.2	c.167T>A	p.Val56Asp	missense_variant	3/18	ENST00000393915.9	NP_001136028.1
HMMR	NM_012484.3	c.167T>A	p.Val56Asp	missense_variant	3/18		NP_036616.2
HMMR	NM_012485.3	c.167T>A	p.Val56Asp	missense_variant	3/17		NP_036617.2
HMMR	NM_001142557.2	c.12+4006T>A		intron_variant			NP_001136029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMMR	ENST00000520345	c.-131T>A		5_prime_UTR_premature_start_codon_gain_variant	3/6	2		ENSP00000428481.1
HMMR	ENST00000393915.9	c.167T>A	p.Val56Asp	missense_variant	3/18	1	NM_001142556.2	ENSP00000377492.4
HMMR	ENST00000520345	c.-131T>A		5_prime_UTR_variant	3/6	2		ENSP00000428481.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ovarian cancer Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University

Jan 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.69
DEOGEN2	Benign	0.13	.;.;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.082	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L;L;L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.88	N;N;N
REVEL	Benign	0.057
Sift	Benign	0.25	T;T;T
Sift4G	Benign	0.65	T;T;T
Polyphen		0.0010	B;P;B
Vest4		0.40
MutPred		0.24		Loss of stability (P = 0.02);Loss of stability (P = 0.02);Loss of stability (P = 0.02);
MVP		0.39
MPC		0.34
ClinPred		0.19	T
GERP RS		0.83
Varity_R		0.23
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.

Other links and lift over

hg19: chr5-162891750;