chr5-163469644-C-A

Variant names:

• chr5-163469644-C-A
• NM_001142556.2:c.277C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001142556.2(HMMR):​c.277C>A​(p.Arg93Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 6.9e-7 (0 hom.)
• Consequence: HMMR NM_001142556.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.93

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.878

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMMR	NM_001142556.2	c.277C>A	p.Arg93Ser	missense_variant	Exon 5 of 18	ENST00000393915.9	NP_001136028.1
HMMR	NM_012484.3	c.274C>A	p.Arg92Ser	missense_variant	Exon 5 of 18		NP_036616.2
HMMR	NM_012485.3	c.229C>A	p.Arg77Ser	missense_variant	Exon 4 of 17		NP_036617.2
HMMR	NM_001142557.2	c.16C>A	p.Arg6Ser	missense_variant	Exon 2 of 15		NP_001136029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMMR	ENST00000393915.9	c.277C>A	p.Arg93Ser	missense_variant	Exon 5 of 18	1	NM_001142556.2	ENSP00000377492.4
HMMR	ENST00000520345	c.-69C>A		5_prime_UTR_variant	Exon 4 of 6	2		ENSP00000428481.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455264 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724162

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: 0.0000117

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	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	.;.;.;T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.70	T;D;T;D
M_CAP	Uncertain	0.096	D
MetaRNN	Pathogenic	0.88	D;D;D;D
MetaSVM	Uncertain	0.21	D
MutationAssessor	Uncertain	2.7	.;.;.;M
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.3	D;D;D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.84
MutPred		0.23		.;.;.;Loss of MoRF binding (P = 0.011);
MVP		0.92
MPC		0.35
ClinPred		0.96	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.80
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.30		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-162896650;