chr5-163467723-A-C

Position:

• chr5-163467723-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001142556.2(HMMR):​c.248A>C​(p.Lys83Thr) variant causes a missense change. 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 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: 4.09

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35544842).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMMR	NM_001142556.2	c.248A>C	p.Lys83Thr	missense_variant	4/18	ENST00000393915.9	NP_001136028.1
HMMR	NM_012484.3	c.245A>C	p.Lys82Thr	missense_variant	4/18		NP_036616.2
HMMR	NM_012485.3	c.226-1918A>C		intron_variant			NP_036617.2
HMMR	NM_001142557.2	c.13-1918A>C		intron_variant			NP_001136029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMMR	ENST00000393915.9	c.248A>C	p.Lys83Thr	missense_variant	4/18	1	NM_001142556.2	ENSP00000377492.4
HMMR	ENST00000520345.5	c.-72-1918A>C		intron_variant		2		ENSP00000428481.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 22

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

Apr 13, 2023

The c.248A>C (p.K83T) alteration is located in exon 4 (coding exon 4) of the HMMR gene. This alteration results from a A to C substitution at nucleotide position 248, causing the lysine (K) at amino acid position 83 to be replaced by a threonine (T). 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	0.16
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	.;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.80	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Uncertain	0.036	D
MutationAssessor	Uncertain	2.7	.;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.5	D;N
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D;T
Sift4G	Uncertain	0.022	D;D
Polyphen		1.0	D;D
Vest4		0.37
MutPred		0.21		.;Loss of ubiquitination at K82 (P = 0.0244);
MVP		0.90
MPC		0.41
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.10
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr5-162894729;