rs1213909019

Variant names:

• chr6-42106902-C-A
• rs1213909019
• NM_001164446.3:c.1010G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-42106902-C-A
• chr6-42106902-C-T

Variant summary

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

The NM_001164446.3(C6orf132):​c.1010G>T​(p.Arg337Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000723 in 1,383,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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. R337Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: C6orf132 NM_001164446.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510

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=0.104225695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C6orf132	NM_001164446.3	c.1010G>T	p.Arg337Leu	missense_variant	Exon 4 of 5	ENST00000341865.9	NP_001157918.1
C6orf132	XM_047419258.1	c.455G>T	p.Arg152Leu	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.1010G>T	p.Arg337Leu	missense_variant	Exon 4 of 5	5	NM_001164446.3	ENSP00000341368.4
C6orf132	ENST00000696229.1	n.*1622G>T		non_coding_transcript_exon_variant	Exon 5 of 6			ENSP00000512495.1
C6orf132	ENST00000696229.1	n.*1622G>T		3_prime_UTR_variant	Exon 5 of 6			ENSP00000512495.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.00000723 AC: 10 AN: 1383826 Hom.: 0 Cov.: 36 AF XY: 0.0000103 AC XY: 7 AN XY: 682680

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000927

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 26

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.091	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.019
Sift	Uncertain	0.011	D
Sift4G	Benign	0.42	T
Vest4		0.19
MutPred		0.26		Gain of ubiquitination at K333 (P = 0.0267);
MVP		0.17
ClinPred		0.73	D
GERP RS		0.95
Varity_R		0.22
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs1213909019; hg19: chr6-42074640;