6-87345169-C-T

Variant names:

• chr6-87345169-C-T
• rs934122897
• NM_001010868.3:c.70C>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.70C>T​(p.Pro24Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,384,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P24A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: C6orf163 NM_001010868.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18
• 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=0.4085408).

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.70C>T	p.Pro24Ser	missense	Exon 1 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.70C>T	p.Pro24Ser	missense	Exon 1 of 5	ENSP00000373575.3	Q5TEZ5
	SMIM8	ENST00000448282.6	TSL:1	n.135+8003C>T		intron	N/A	ENSP00000476881.1	V9GYL2
	SMIM8	ENST00000369572.3	TSL:5	n.13+22537C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1384410 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 683096

African (AFR) AF: 0.00 AC: 0 AN: 31566

American (AMR) AF: 0.00 AC: 0 AN: 35610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 35702

South Asian (SAS) AF: 0.00 AC: 0 AN: 79110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35000

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078660

Other (OTH) AF: 0.00 AC: 0 AN: 57900

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.071	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.2
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.57
MutPred		0.30		Gain of helix (P = 0.0854)
MVP		0.32
ClinPred		0.99	D
GERP RS		5.5
PromoterAI		-0.00050	Neutral
Varity_R		0.28
gMVP		0.52
Mutation Taster		=96/4	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: rs934122897; hg19: chr6-88054887; COSMIC: COSV104566184; COSMIC: COSV104566184;