chr6-165300472-A-C

Position:

• chr6-165300472-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144980.4(C6orf118):​c.768T>G​(p.Ile256Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,607,492 control chromosomes in the GnomAD database, including 121,026 homozygotes. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.48 (19750 hom., cov: 32)
  • Exomes 𝑓: 0.36 (101276 hom.)
• Consequence: C6orf118 NM_144980.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

Genes affected

C6orf118 (HGNC:21233): (chromosome 6 open reading frame 118)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.6664145E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C6orf118	NM_144980.4	c.768T>G	p.Ile256Met	missense_variant	3/9	ENST00000230301.9	NP_659417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C6orf118	ENST00000230301.9	c.768T>G	p.Ile256Met	missense_variant	3/9	1	NM_144980.4	ENSP00000230301.8

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72513 AN: 151906 Hom.: 19695 Cov.: 32

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.429

GnomAD3 exomes AF: 0.390 AC: 96856 AN: 248658 Hom.: 20537 AF XY: 0.383 AC XY: 51570 AN XY: 134572

Gnomad AFR exome AF: 0.758

Gnomad AMR exome AF: 0.371

Gnomad ASJ exome AF: 0.368

Gnomad EAS exome AF: 0.203

Gnomad SAS exome AF: 0.405

Gnomad FIN exome AF: 0.474

Gnomad NFE exome AF: 0.355

Gnomad OTH exome AF: 0.381

GnomAD4 exome AF: 0.364 AC: 530410 AN: 1455468 Hom.: 101276 Cov.: 34 AF XY: 0.365 AC XY: 264291 AN XY: 724228

Gnomad4 AFR exome AF: 0.772

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.364

Gnomad4 EAS exome AF: 0.252

Gnomad4 SAS exome AF: 0.401

Gnomad4 FIN exome AF: 0.471

Gnomad4 NFE exome AF: 0.347

Gnomad4 OTH exome AF: 0.383

GnomAD4 genome AF: 0.478 AC: 72623 AN: 152024 Hom.: 19750 Cov.: 32 AF XY: 0.482 AC XY: 35777 AN XY: 74302

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.429

Alfa AF: 0.370 Hom.: 22451

Bravo AF: 0.477

TwinsUK AF: 0.347 AC: 1285

ALSPAC AF: 0.337 AC: 1299

ESP6500AA AF: 0.747 AC: 3290

ESP6500EA AF: 0.349 AC: 2999

ExAC AF: 0.396 AC: 48013

Asia WGS AF: 0.359 AC: 1248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.057
DANN	Benign	0.78
DEOGEN2	Benign	0.0080	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.0000017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.090
Sift	Benign	0.14	T
Sift4G	Benign	0.10	T
Polyphen		0.99	D
Vest4		0.059
MPC		0.074
ClinPred		0.035	T
GERP RS		-10
Varity_R		0.055
gMVP		0.13

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: rs510579; hg19: chr6-165713961; COSMIC: COSV57813552;