rs299290

Positions:

• chr5-163475510-T-A
• chr5-163475510-T-C
• chr5-163475510-T-G

Variant summary

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

The NM_001142556.2(HMMR):​c.1106T>A​(p.Val369Asp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HMMR NM_001142556.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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

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=0.052818567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMMR	NM_001142556.2	c.1106T>A	p.Val369Asp	missense_variant	11/18	ENST00000393915.9
HMMR	NM_012484.3	c.1103T>A	p.Val368Asp	missense_variant	11/18
HMMR	NM_012485.3	c.1058T>A	p.Val353Asp	missense_variant	10/17
HMMR	NM_001142557.2	c.845T>A	p.Val282Asp	missense_variant	8/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMMR	ENST00000393915.9	c.1106T>A	p.Val369Asp	missense_variant	11/18	1	NM_001142556.2	A2
HMMR	ENST00000358715.3	c.1103T>A	p.Val368Asp	missense_variant	11/18	1		P4
HMMR	ENST00000353866.7	c.1058T>A	p.Val353Asp	missense_variant	10/17	1
HMMR	ENST00000432118.6	c.845T>A	p.Val282Asp	missense_variant	8/15	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1457302 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725358

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Benign	0.80
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.84	T;T;T;T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.053	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.071
Sift	Uncertain	0.011	D;D;D;D
Sift4G	Benign	0.097	T;T;T;T
Polyphen		0.35	B;B;B;B
Vest4		0.18
MutPred		0.093		.;.;.;Loss of methylation at K369 (P = 0.0431);
MVP		0.35
MPC		0.10
ClinPred		0.10	T
GERP RS		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.13

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

LitVar

Other links and lift over

dbSNP: rs299290; hg19: chr5-162902516;