5-163475510-T-G

Variant names:

• chr5-163475510-T-G
• rs299290
• NM_001142556.2:c.1106T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142556.2(HMMR):​c.1106T>G​(p.Val369Gly) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HMMR NM_001142556.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• Publications: 47 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05132836).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMMR	NM_001142556.2	MANE Select	c.1106T>G	p.Val369Gly	missense	Exon 11 of 18	NP_001136028.1
	HMMR	NM_012484.3		c.1103T>G	p.Val368Gly	missense	Exon 11 of 18	NP_036616.2
	HMMR	NM_012485.3		c.1058T>G	p.Val353Gly	missense	Exon 10 of 17	NP_036617.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMMR	ENST00000393915.9	TSL:1 MANE Select	c.1106T>G	p.Val369Gly	missense	Exon 11 of 18	ENSP00000377492.4
	HMMR	ENST00000358715.3	TSL:1	c.1103T>G	p.Val368Gly	missense	Exon 11 of 18	ENSP00000351554.3
	HMMR	ENST00000353866.7	TSL:1	c.1058T>G	p.Val353Gly	missense	Exon 10 of 17	ENSP00000185942.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.29	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.027
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.061
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.11	T
Polyphen		0.35	B
Vest4		0.066
MutPred		0.12		Loss of stability (P = 0.0234)
MVP		0.34
MPC		0.076
ClinPred		0.10	T
GERP RS		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.11
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs299290; hg19: chr5-162902516;