6-42105519-C-T

Variant names:

• chr6-42105519-C-T
• NM_001164446.3:c.2393G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164446.3(C6orf132):​c.2393G>A​(p.Gly798Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: C6orf132 NM_001164446.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.361

Genes affected

C6orf132 (HGNC:21288): (chromosome 6 open reading frame 132)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09241673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C6orf132	NM_001164446.3	c.2393G>A	p.Gly798Glu	missense_variant	Exon 4 of 5	ENST00000341865.9	NP_001157918.1
C6orf132	XM_047419258.1	c.1838G>A	p.Gly613Glu	missense_variant	Exon 3 of 4		XP_047275214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C6orf132	ENST00000341865.9	c.2393G>A	p.Gly798Glu	missense_variant	Exon 4 of 5	5	NM_001164446.3	ENSP00000341368.4
C6orf132	ENST00000696229.1	n.*3005G>A		non_coding_transcript_exon_variant	Exon 5 of 6			ENSP00000512495.1
C6orf132	ENST00000696229.1	n.*3005G>A		3_prime_UTR_variant	Exon 5 of 6			ENSP00000512495.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 78

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 14, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2393G>A (p.G798E) alteration is located in exon 4 (coding exon 4) of the C6orf132 gene. This alteration results from a G to A substitution at nucleotide position 2393, causing the glycine (G) at amino acid position 798 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.5
DANN	Uncertain	0.98
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.14	N
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.030
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0040	D
Vest4		0.065
MutPred		0.16		Gain of solvent accessibility (P = 0.024);
MVP		0.15
ClinPred		0.23	T
GERP RS		0.18
Varity_R		0.20
gMVP		0.077

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-42073257;