rs62624492

Variant names:

• chr7-148590928-G-T
• rs62624492
• NM_145304.4:c.3G>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PVS1_Supporting 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
• Publications: 11 publications found

Genes affected

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

ENSG00000287636 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 76 codons. Genomic position: 148614063. Lost 0.423 part of the original CDS.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0824 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145304.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C7orf33	NM_145304.4	MANE Select	c.3G>T	p.Met1?	start_lost	Exon 1 of 3	NP_660347.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C7orf33	ENST00000307003.3	TSL:1 MANE Select	c.3G>T	p.Met1?	start_lost	Exon 1 of 3	ENSP00000304071.2
	ENSG00000287636	ENST00000660070.1		n.122-4588C>A		intron	N/A
	ENSG00000287636	ENST00000686491.1		n.250-2893C>A		intron	N/A

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

GnomAD2 exomes AF: 0.0420 AC: 10546 AN: 251364 AF XY: 0.0412

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 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

African (AFR) AF: 0.00956 AC: 320 AN: 33478

American (AMR) AF: 0.109 AC: 4854 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0425 AC: 1110 AN: 26136

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39698

South Asian (SAS) AF: 0.0508 AC: 4379 AN: 86250

European-Finnish (FIN) AF: 0.0159 AC: 847 AN: 53412

Middle Eastern (MID) AF: 0.0451 AC: 260 AN: 5764

European-Non Finnish (NFE) AF: 0.0358 AC: 39836 AN: 1111780

Other (OTH) AF: 0.0336 AC: 2027 AN: 60378

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

African (AFR) AF: 0.0108 AC: 450 AN: 41556

American (AMR) AF: 0.0863 AC: 1319 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0397 AC: 138 AN: 3472

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5176

South Asian (SAS) AF: 0.0455 AC: 219 AN: 4816

European-Finnish (FIN) AF: 0.0145 AC: 154 AN: 10594

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0341 AC: 2317 AN: 68000

Other (OTH) AF: 0.0289 AC: 61 AN: 2114

Alfa AF: 0.0340 Hom.: 350

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 v4.9

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
PhyloP100		-0.65
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
PromoterAI		0.0066	Neutral
Varity_R		0.45
gMVP		0.052
Mutation Taster		=198/2	polymorphism (auto)

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: rs62624492; hg19: chr7-148288020; COSMIC: COSV107395925;