chr6-87365133-C-T

Variant names:

• chr6-87365133-C-T
• rs1777627284
• NM_001010868.3:c.727C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010868.3. 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
	C6orf163	NM_001010868.3	MANE Select	c.727C>T	p.His243Tyr	missense	Exon 5 of 5	NP_001010868.2	Q5TEZ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C6orf163	ENST00000388923.5	TSL:5 MANE Select	c.727C>T	p.His243Tyr	missense	Exon 5 of 5	ENSP00000373575.3	Q5TEZ5
	C6orf163	ENST00000608891.1	TSL:1	n.282C>T		non_coding_transcript_exon	Exon 2 of 2
	SMIM8	ENST00000448282.6	TSL:1	n.136-6460C>T		intron	N/A	ENSP00000476881.1	V9GYL2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.39	T
MetaSVM	Uncertain	0.089	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.5
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.013	D
Sift4G	Benign	0.081	T
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
Mutation Taster		=89/11	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: rs1777627284; hg19: chr6-88074851;