NM_001129742.2:c.620A>C

Variant names:

• chr10-103473628-T-G
• rs201728558
• NM_001129742.2:c.620A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001129742.2(CALHM3):​c.620A>C​(p.Gln207Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,398,980 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Q207R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: CALHM3 NM_001129742.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.73
• Publications: 4 publications found

Genes affected

CALHM3 (HGNC:23458): (calcium homeostasis modulator 3) Predicted to enable cation channel activity. Predicted to be involved in ATP transport. Predicted to be located in basolateral plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALHM3	NM_001129742.2	c.620A>C	p.Gln207Pro	missense_variant	Exon 3 of 3	ENST00000369783.4	NP_001123214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALHM3	ENST00000369783.4	c.620A>C	p.Gln207Pro	missense_variant	Exon 3 of 3	1	NM_001129742.2	ENSP00000358798.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000646 AC: 1 AN: 154780 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.0000168

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000186 AC: 26 AN: 1398980 Hom.: 0 Cov.: 34 AF XY: 0.0000203 AC XY: 14 AN XY: 690020

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.0000222 AC: 24 AN: 1078984

Other (OTH) AF: 0.0000345 AC: 2 AN: 58004

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0099	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		5.7
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.38	N
REVEL	Benign	0.29
Sift	Benign	0.15	T
Sift4G	Uncertain	0.0070	D
Vest4		0.65
MutPred		0.54		Gain of loop (P = 0.0851);
MVP		0.15
ClinPred		0.87	D
GERP RS		5.7
Varity_R		0.28
gMVP		0.62
Mutation Taster		=37/63	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201728558; hg19: chr10-105233385;