19-53912937-A-T

Variant names:

• chr19-53912937-A-T
• rs748295737
• NM_031896.5:c.106A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_031896.5(CACNG7):​c.106A>T​(p.Met36Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. M36V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CACNG7 NM_031896.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 1 publications found

Genes affected

CACNG7 (HGNC:13626): (calcium voltage-gated channel auxiliary subunit gamma 7) The protein encoded by this gene is a type II transmembrane AMPA receptor regulatory protein (TARP). TARPs regulate both trafficking and channel gating of the AMPA receptors. This gene is part of a functionally diverse eight-member protein subfamily of the PMP-22/EMP/MP20 family and is located in a cluster with two family members, a type I TARP and a calcium channel gamma subunit. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 1.6455 (below the threshold of 3.09). Trascript score misZ: 1.8969 (below the threshold of 3.09).
• BP4: Computational evidence support a benign effect (MetaRNN=0.10217303).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031896.5. 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
	CACNG7	NM_031896.5	MANE Select	c.106A>T	p.Met36Leu	missense	Exon 2 of 6	NP_114102.2
	CACNG7	NM_001384801.1		c.106A>T	p.Met36Leu	missense	Exon 2 of 5	NP_001371730.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNG7	ENST00000391767.6	TSL:5 MANE Select	c.106A>T	p.Met36Leu	missense	Exon 2 of 6	ENSP00000375647.1	P62955
	CACNG7	ENST00000222212.6	TSL:1	c.106A>T	p.Met36Leu	missense	Exon 1 of 5	ENSP00000222212.2	P62955
	CACNG7	ENST00000391766.1	TSL:1	c.106A>T	p.Met36Leu	missense	Exon 1 of 4	ENSP00000375646.1	A0A0C4DFY2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251262 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461846 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.10
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.082	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	-0.98	N
PhyloP100		1.2
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.42	N
REVEL	Uncertain	0.37
Sift	Benign	0.18	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.23
MutPred		0.56		Gain of helix (P = 0.062)
MVP		0.74
MPC		0.75
ClinPred		0.18	T
GERP RS		4.3
PromoterAI		-0.0082	Neutral
Varity_R		0.19
gMVP		0.82
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs748295737; hg19: chr19-54416191;