5-163482710-C-T

Variant names:

• chr5-163482710-C-T
• rs299295
• NM_001142556.2:c.1454C>T

Variant summary

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

The NM_001142556.2(HMMR):​c.1454C>T​(p.Ala485Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,609,806 control chromosomes in the GnomAD database, including 46,728 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A485T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.25 (4957 hom., cov: 32)
  • Exomes 𝑓: 0.23 (41771 hom.)
• Consequence: HMMR NM_001142556.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30
• Publications: 32 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]

HMMR-AS1 (HGNC:49149): (HMMR antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0045486987).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMMR	NM_001142556.2	MANE Select	c.1454C>T	p.Ala485Val	missense	Exon 13 of 18	NP_001136028.1	O75330-3
	HMMR	NM_012484.3		c.1451C>T	p.Ala484Val	missense	Exon 13 of 18	NP_036616.2	O75330-1
	HMMR	NM_012485.3		c.1406C>T	p.Ala469Val	missense	Exon 12 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.1454C>T	p.Ala485Val	missense	Exon 13 of 18	ENSP00000377492.4	O75330-3
	HMMR	ENST00000358715.3	TSL:1	c.1451C>T	p.Ala484Val	missense	Exon 13 of 18	ENSP00000351554.3	O75330-1
	HMMR	ENST00000353866.7	TSL:1	c.1406C>T	p.Ala469Val	missense	Exon 12 of 17	ENSP00000185942.6	O75330-2

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37924 AN: 151684 Hom.: 4953 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0621

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.232

GnomAD2 exomes AF: 0.226 AC: 56686 AN: 251072 AF XY: 0.231

Gnomad AFR exome AF: 0.289

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.216

Gnomad EAS exome AF: 0.0664

Gnomad FIN exome AF: 0.282

Gnomad NFE exome AF: 0.243

Gnomad OTH exome AF: 0.235

GnomAD4 exome AF: 0.234 AC: 341599 AN: 1458004 Hom.: 41771 Cov.: 31 AF XY: 0.235 AC XY: 170653 AN XY: 725436

African (AFR) AF: 0.294 AC: 9817 AN: 33382

American (AMR) AF: 0.164 AC: 7342 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 5688 AN: 26104

East Asian (EAS) AF: 0.0554 AC: 2199 AN: 39668

South Asian (SAS) AF: 0.262 AC: 22562 AN: 86084

European-Finnish (FIN) AF: 0.281 AC: 15025 AN: 53388

Middle Eastern (MID) AF: 0.236 AC: 1362 AN: 5760

European-Non Finnish (NFE) AF: 0.238 AC: 263581 AN: 1108660

Other (OTH) AF: 0.233 AC: 14023 AN: 60276

GnomAD4 genome AF: 0.250 AC: 37935 AN: 151802 Hom.: 4957 Cov.: 32 AF XY: 0.249 AC XY: 18427 AN XY: 74142

African (AFR) AF: 0.297 AC: 12281 AN: 41378

American (AMR) AF: 0.207 AC: 3167 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 772 AN: 3464

East Asian (EAS) AF: 0.0620 AC: 321 AN: 5174

South Asian (SAS) AF: 0.258 AC: 1238 AN: 4806

European-Finnish (FIN) AF: 0.283 AC: 2964 AN: 10486

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.242 AC: 16413 AN: 67922

Other (OTH) AF: 0.238 AC: 501 AN: 2106

Alfa AF: 0.238 Hom.: 19282

Bravo AF: 0.241

TwinsUK AF: 0.236 AC: 875

ALSPAC AF: 0.235 AC: 904

ESP6500AA AF: 0.290 AC: 1278

ESP6500EA AF: 0.238 AC: 2046

ExAC AF: 0.233 AC: 28232

Asia WGS AF: 0.184 AC: 641 AN: 3478

EpiCase AF: 0.243

EpiControl AF: 0.237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
DANN	Benign	0.53
DEOGEN2	Benign	0.21	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.043	T
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.5	N
PhyloP100		2.3
PrimateAI	Benign	0.32	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	0.80	T
Polyphen		0.0	B
Vest4		0.018
MPC		0.059
ClinPred		0.0031	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.017
gMVP		0.040
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs299295; hg19: chr5-162909716; COSMIC: COSV62374535; COSMIC: COSV62374535;