5-163475510-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142556.2(HMMR):​c.1106T>C​(p.Val369Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,606,324 control chromosomes in the GnomAD database, including 56,929 homozygotes. 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: 𝑓 0.28 (6080 hom., cov: 32)
  • Exomes 𝑓: 0.26 (50849 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.9145012E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

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>C	p.Val369Ala	missense	Exon 11 of 18	NP_001136028.1
	HMMR	NM_012484.3		c.1103T>C	p.Val368Ala	missense	Exon 11 of 18	NP_036616.2
	HMMR	NM_012485.3		c.1058T>C	p.Val353Ala	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>C	p.Val369Ala	missense	Exon 11 of 18	ENSP00000377492.4
	HMMR	ENST00000358715.3	TSL:1	c.1103T>C	p.Val368Ala	missense	Exon 11 of 18	ENSP00000351554.3
	HMMR	ENST00000353866.7	TSL:1	c.1058T>C	p.Val353Ala	missense	Exon 10 of 17	ENSP00000185942.6

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42387 AN: 151794 Hom.: 6066 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.250

GnomAD2 exomes AF: 0.283 AC: 70707 AN: 250082 AF XY: 0.280

Gnomad AFR exome AF: 0.300

Gnomad AMR exome AF: 0.298

Gnomad ASJ exome AF: 0.217

Gnomad EAS exome AF: 0.505

Gnomad FIN exome AF: 0.284

Gnomad NFE exome AF: 0.250

Gnomad OTH exome AF: 0.262

GnomAD4 exome AF: 0.258 AC: 375345 AN: 1454410 Hom.: 50849 Cov.: 29 AF XY: 0.258 AC XY: 187026 AN XY: 724010

African (AFR) AF: 0.304 AC: 10149 AN: 33332

American (AMR) AF: 0.294 AC: 13063 AN: 44372

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 5729 AN: 26034

East Asian (EAS) AF: 0.505 AC: 19919 AN: 39470

South Asian (SAS) AF: 0.276 AC: 23666 AN: 85754

European-Finnish (FIN) AF: 0.282 AC: 15034 AN: 53298

Middle Eastern (MID) AF: 0.249 AC: 1432 AN: 5748

European-Non Finnish (NFE) AF: 0.245 AC: 270573 AN: 1106384

Other (OTH) AF: 0.263 AC: 15780 AN: 60018

GnomAD4 genome AF: 0.279 AC: 42416 AN: 151914 Hom.: 6080 Cov.: 32 AF XY: 0.282 AC XY: 20950 AN XY: 74228

African (AFR) AF: 0.308 AC: 12745 AN: 41436

American (AMR) AF: 0.283 AC: 4316 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3468

East Asian (EAS) AF: 0.497 AC: 2557 AN: 5146

South Asian (SAS) AF: 0.281 AC: 1353 AN: 4808

European-Finnish (FIN) AF: 0.281 AC: 2957 AN: 10532

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16866 AN: 67948

Other (OTH) AF: 0.257 AC: 543 AN: 2112

Alfa AF: 0.259 Hom.: 22836

Bravo AF: 0.279

TwinsUK AF: 0.239 AC: 888

ALSPAC AF: 0.242 AC: 932

ESP6500AA AF: 0.300 AC: 1323

ESP6500EA AF: 0.245 AC: 2105

ExAC AF: 0.283 AC: 34405

Asia WGS AF: 0.360 AC: 1252 AN: 3476

EpiCase AF: 0.251

EpiControl AF: 0.243

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	15
DANN	Benign	0.54
DEOGEN2	Benign	0.21	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.00019	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.027
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.065
Sift	Benign	0.21	T
Sift4G	Benign	0.19	T
Polyphen		0.047	B
Vest4		0.038
MPC		0.071
ClinPred		0.0072	T
GERP RS		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.030
gMVP		0.061
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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; COSMIC: COSV62373893; COSMIC: COSV62373893;