5-163484123-GCA-ACG

Variant names:

• chr5-163484123-GCA-ACG
• NM_001142556.2:c.1840_1842delGCAinsACG
• HMMR p.Ala614Thr

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001142556.2(HMMR):​c.1840_1842delGCAinsACG​(p.Ala614Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HMMR NM_001142556.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.52
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.1840_1842delGCAinsACG	p.Ala614Thr	missense	N/A	NP_001136028.1	O75330-3
	HMMR	NM_012484.3		c.1837_1839delGCAinsACG	p.Ala613Thr	missense	N/A	NP_036616.2	O75330-1
	HMMR	NM_012485.3		c.1792_1794delGCAinsACG	p.Ala598Thr	missense	N/A	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.1840_1842delGCAinsACG	p.Ala614Thr	missense	N/A	ENSP00000377492.4	O75330-3
	HMMR	ENST00000358715.3	TSL:1	c.1837_1839delGCAinsACG	p.Ala613Thr	missense	N/A	ENSP00000351554.3	O75330-1
	HMMR	ENST00000353866.7	TSL:1	c.1792_1794delGCAinsACG	p.Ala598Thr	missense	N/A	ENSP00000185942.6	O75330-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-162911129;