rs62624492

Positions:

• chr7-148590928-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 8P and 8B. PVS1 BA1

The NM_145304.4(C7orf33):​c.3G>T​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 1,613,828 control chromosomes in the GnomAD database, including 1,328 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.031 (122 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1206 hom.)
• Consequence: C7orf33 NM_145304.4 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.652

Genes affected

C7orf33 (HGNC:21724): (chromosome 7 open reading frame 33)

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C7orf33	NM_145304.4	c.3G>T	p.Met1?	start_lost	1/3	ENST00000307003.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C7orf33	ENST00000307003.3	c.3G>T	p.Met1?	start_lost	1/3	1	NM_145304.4	P1
	ENST00000660070.1	n.122-4588C>A		intron_variant, non_coding_transcript_variant
	ENST00000686491.1	n.250-2893C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0310 AC: 4716 AN: 152102 Hom.: 121 Cov.: 32

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.0397

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0450

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0341

Gnomad OTH AF: 0.0292

GnomAD3 exomes AF: 0.0420 AC: 10546 AN: 251364 Hom.: 341 AF XY: 0.0412 AC XY: 5596 AN XY: 135862

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.0414

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0511

Gnomad FIN exome AF: 0.0160

Gnomad NFE exome AF: 0.0349

Gnomad OTH exome AF: 0.0434

GnomAD4 exome AF: 0.0367 AC: 53642 AN: 1461608 Hom.: 1206 Cov.: 31 AF XY: 0.0369 AC XY: 26858 AN XY: 727112

Gnomad4 AFR exome AF: 0.00956

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.0425

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0508

Gnomad4 FIN exome AF: 0.0159

Gnomad4 NFE exome AF: 0.0358

Gnomad4 OTH exome AF: 0.0336

GnomAD4 genome AF: 0.0310 AC: 4724 AN: 152220 Hom.: 122 Cov.: 32 AF XY: 0.0313 AC XY: 2332 AN XY: 74422

Gnomad4 AFR AF: 0.0108

Gnomad4 AMR AF: 0.0863

Gnomad4 ASJ AF: 0.0397

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0455

Gnomad4 FIN AF: 0.0145

Gnomad4 NFE AF: 0.0341

Gnomad4 OTH AF: 0.0289

Alfa AF: 0.0343 Hom.: 174

Bravo AF: 0.0350

TwinsUK AF: 0.0356 AC: 132

ALSPAC AF: 0.0402 AC: 155

ESP6500AA AF: 0.0123 AC: 54

ESP6500EA AF: 0.0338 AC: 291

ExAC AF: 0.0390 AC: 4738

Asia WGS AF: 0.0160 AC: 57 AN: 3478

EpiCase AF: 0.0327

EpiControl AF: 0.0340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.8
DANN	Benign	0.62
DEOGEN2	Benign	0.056	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.014	N
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Polyphen		0.0050	B
Vest4		0.072
MutPred		0.83		Gain of catalytic residue at M1 (P = 0.0523);
ClinPred		0.014	T
GERP RS		-3.8
Varity_R		0.45
gMVP		0.052

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: rs62624492; hg19: chr7-148288020;