5-163483120-C-T

Variant names:

• chr5-163483120-C-T
• rs200981355
• NM_001142556.2:c.1633C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001142556.2(HMMR):​c.1633C>T​(p.Leu545Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000311 in 1,612,482 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00032 (1 hom.)
• Consequence: HMMR NM_001142556.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.53
• Publications: 4 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1612787).
• BS2: High AC in GnomAd4 at 32 AD gene.

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.1633C>T	p.Leu545Phe	missense	Exon 14 of 18	NP_001136028.1	O75330-3
	HMMR	NM_012484.3		c.1630C>T	p.Leu544Phe	missense	Exon 14 of 18	NP_036616.2	O75330-1
	HMMR	NM_012485.3		c.1585C>T	p.Leu529Phe	missense	Exon 13 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.1633C>T	p.Leu545Phe	missense	Exon 14 of 18	ENSP00000377492.4	O75330-3
	HMMR	ENST00000358715.3	TSL:1	c.1630C>T	p.Leu544Phe	missense	Exon 14 of 18	ENSP00000351554.3	O75330-1
	HMMR	ENST00000353866.7	TSL:1	c.1585C>T	p.Leu529Phe	missense	Exon 13 of 17	ENSP00000185942.6	O75330-2

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152142 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000144 AC: 36 AN: 249196 AF XY: 0.000170

Gnomad AFR exome AF: 0.0000628

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000310

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000321 AC: 469 AN: 1460340 Hom.: 1 Cov.: 31 AF XY: 0.000326 AC XY: 237 AN XY: 726548

African (AFR) AF: 0.0000900 AC: 3 AN: 33330

American (AMR) AF: 0.00 AC: 0 AN: 44380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000410 AC: 456 AN: 1111394

Other (OTH) AF: 0.000166 AC: 10 AN: 60332

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152142 Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16 AN XY: 74328

African (AFR) AF: 0.0000724 AC: 3 AN: 41436

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000262 Hom.: 0

Bravo AF: 0.000170

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000157 AC: 19

EpiCase AF: 0.000436

EpiControl AF: 0.000296

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	0.16
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.66	D
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.5
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.079
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.030	D
Polyphen		0.65	P
Vest4		0.29
MVP		0.82
MPC		0.39
ClinPred		0.35	T
GERP RS		5.3
Varity_R		0.28
gMVP		0.40
Mutation Taster		=63/37	polymorphism

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: rs200981355; hg19: chr5-162910126;