5-163483133-A-T

Position:

• chr5-163483133-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142556.2(HMMR):​c.1646A>T​(p.Glu549Val) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HMMR NM_001142556.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.215

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-AS1 (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=0.06198761).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMMR	NM_001142556.2	c.1646A>T	p.Glu549Val	missense_variant	14/18	ENST00000393915.9	NP_001136028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMMR	ENST00000393915.9	c.1646A>T	p.Glu549Val	missense_variant	14/18	1	NM_001142556.2	ENSP00000377492.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.1646A>T (p.E549V) alteration is located in exon 14 (coding exon 14) of the HMMR gene. This alteration results from a A to T substitution at nucleotide position 1646, causing the glutamic acid (E) at amino acid position 549 to be replaced by a valine (V). 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	0.15
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.24	.;.;.;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.77	T;T;T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.062	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	.;.;.;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.045
Sift	Benign	0.28	T;T;T;T
Sift4G	Benign	0.26	T;T;T;T
Polyphen		0.029	B;B;B;B
Vest4		0.26
MutPred		0.21		.;.;.;Gain of MoRF binding (P = 0.0604);
MVP		0.34
MPC		0.077
ClinPred		0.095	T
GERP RS		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.052
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-162910139;