5-163464753-A-T

Variant names:

• chr5-163464753-A-T
• rs1013997641
• NM_001142556.2:c.176A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001142556.2(HMMR):​c.176A>T​(p.Asp59Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,658 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HMMR NM_001142556.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.26
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142556.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMMR	NM_001142556.2	MANE Select	c.176A>T	p.Asp59Val	missense	Exon 3 of 18	NP_001136028.1	O75330-3
	HMMR	NM_012484.3		c.176A>T	p.Asp59Val	missense	Exon 3 of 18	NP_036616.2	O75330-1
	HMMR	NM_012485.3		c.176A>T	p.Asp59Val	missense	Exon 3 of 17	NP_036617.2	O75330-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMMR	ENST00000393915.9	TSL:1 MANE Select	c.176A>T	p.Asp59Val	missense	Exon 3 of 18	ENSP00000377492.4	O75330-3
	HMMR	ENST00000358715.3	TSL:1	c.176A>T	p.Asp59Val	missense	Exon 3 of 18	ENSP00000351554.3	O75330-1
	HMMR	ENST00000353866.7	TSL:1	c.176A>T	p.Asp59Val	missense	Exon 3 of 17	ENSP00000185942.6	O75330-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460658 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726700

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111070

Other (OTH) AF: 0.00 AC: 0 AN: 60358

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.3
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.18
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.96	D
Vest4		0.51
MutPred		0.19		Loss of helix (P = 0.0068)
MVP		0.75
MPC		0.43
ClinPred		0.96	D
GERP RS		5.2
Varity_R		0.20
gMVP		0.28
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs1013997641; hg19: chr5-162891759;