7-1010065-G-C

Variant names:

• chr7-1010065-G-C
• rs1405310498
• NM_001318252.2:c.208C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001318252.2(C7orf50):​c.208C>G​(p.Leu70Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: C7orf50 NM_001318252.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61

Genes affected

C7orf50 (HGNC:22421): (chromosome 7 open reading frame 50) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13979512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C7orf50	NM_001318252.2	c.208C>G	p.Leu70Val	missense_variant	Exon 3 of 5	ENST00000397098.8	NP_001305181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C7orf50	ENST00000397098.8	c.208C>G	p.Leu70Val	missense_variant	Exon 3 of 5	1	NM_001318252.2	ENSP00000380286.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460134 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726434

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 23, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.208C>G (p.L70V) alteration is located in exon 3 (coding exon 2) of the C7orf50 gene. This alteration results from a C to G substitution at nucleotide position 208, causing the leucine (L) at amino acid position 70 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T;T;T;T;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.79	.;T;.;T;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.6	L;L;L;.;.
PROVEAN	Benign	-1.6	N;N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.043	D;D;D;T;D
Sift4G	Uncertain	0.013	D;D;D;D;.
Polyphen		0.20	B;B;B;.;.
Vest4		0.12
MutPred		0.16		Gain of methylation at K71 (P = 0.0331);Gain of methylation at K71 (P = 0.0331);Gain of methylation at K71 (P = 0.0331);.;Gain of methylation at K71 (P = 0.0331);
MVP		0.59
MPC		0.050
ClinPred		0.16	T
GERP RS		3.8
Varity_R		0.14
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1405310498; hg19: chr7-1049701;