6-42107053-C-A

Variant names:

• chr6-42107053-C-A
• rs748254976
• NM_001164446.3:c.859G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001164446.3(C6orf132):​c.859G>T​(p.Ala287Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000074 in 1,351,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. A287T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: C6orf132 NM_001164446.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494
• Publications: 0 publications found

Genes affected

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

C6orf132 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040390015).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164446.3. 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
	C6orf132	NM_001164446.3	MANE Select	c.859G>T	p.Ala287Ser	missense	Exon 4 of 5	NP_001157918.1	Q5T0Z8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C6orf132	ENST00000341865.9	TSL:5 MANE Select	c.859G>T	p.Ala287Ser	missense	Exon 4 of 5	ENSP00000341368.4	Q5T0Z8-1
	C6orf132	ENST00000696229.1		n.*1471G>T		non_coding_transcript_exon	Exon 5 of 6	ENSP00000512495.1	Q5T0Z8-2
	C6orf132	ENST00000696229.1		n.*1471G>T		3_prime_UTR	Exon 5 of 6	ENSP00000512495.1	Q5T0Z8-2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 7.40e-7 AC: 1 AN: 1351110 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 662092

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30394

American (AMR) AF: 0.00 AC: 0 AN: 31678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23476

East Asian (EAS) AF: 0.00 AC: 0 AN: 35150

South Asian (SAS) AF: 0.0000131 AC: 1 AN: 76084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34166

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5498

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1058428

Other (OTH) AF: 0.00 AC: 0 AN: 56236

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.45
DANN	Benign	0.73
DEOGEN2	Benign	0.00087	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.49
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.026
Sift	Benign	0.31	T
Sift4G	Benign	0.77	T
Vest4		0.035
MutPred		0.16		Gain of phosphorylation at A287 (P = 0.0108)
MVP		0.014
ClinPred		0.034	T
GERP RS		0.67
Varity_R		0.040
gMVP		0.047
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs748254976; hg19: chr6-42074791;