6-87365133-C-T

Position:

• chr6-87365133-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001010868.3(C6orf163):​c.727C>T​(p.His243Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: C6orf163 NM_001010868.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.54

Genes affected

C6orf163 (HGNC:21403): (chromosome 6 open reading frame 163)

SMIM8 (HGNC:21401): (small integral membrane protein 8) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38821343).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C6orf163	NM_001010868.3	c.727C>T	p.His243Tyr	missense_variant	5/5	ENST00000388923.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C6orf163	ENST00000388923.5	c.727C>T	p.His243Tyr	missense_variant	5/5	5	NM_001010868.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 16, 2021

The c.727C>T (p.H243Y) alteration is located in exon 5 (coding exon 5) of the C6orf163 gene. This alteration results from a C to T substitution at nucleotide position 727, causing the histidine (H) at amino acid position 243 to be replaced by a tyrosine (Y). 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	0.16
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Uncertain	0.089	D
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	0.70	D;D
PROVEAN	Uncertain	-2.8	D;.
REVEL	Uncertain	0.42
Sift	Uncertain	0.013	D;.
Sift4G	Benign	0.081	T;D
Vest4		0.48
MutPred		0.36		Loss of disorder (P = 0.0413);.;
MVP		0.95
ClinPred		0.97	D
GERP RS		6.2
Varity_R		0.40
gMVP		0.87

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: rs1777627284; hg19: chr6-88074851;