rs146608974

Variant names:

• chr4-7061167-C-A
• NM_025196.4:c.349G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-7061167-C-A
• chr4-7061167-C-G
• chr4-7061167-C-T

Variant summary

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

The NM_025196.4(GRPEL1):​c.349G>T​(p.Val117Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,254 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V117I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GRPEL1 NM_025196.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.14

Genes affected

GRPEL1 (HGNC:19696): (GrpE like 1, mitochondrial) Enables identical protein binding activity and unfolded protein binding activity. Predicted to be involved in protein import into mitochondrial matrix. Located in mitochondrial matrix and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRPEL1	NM_025196.4	c.349G>T	p.Val117Phe	missense_variant	Exon 4 of 4	ENST00000264954.5	NP_079472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRPEL1	ENST00000264954.5	c.349G>T	p.Val117Phe	missense_variant	Exon 4 of 4	1	NM_025196.4	ENSP00000264954.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461254 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726944

Gnomad4 AFR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.028
Eigen_PC	Benign	-0.016
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.87	P
Vest4		0.25
MutPred		0.57		Gain of catalytic residue at V117 (P = 0.0112);
MVP		0.31
MPC		0.75
ClinPred		0.98	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.60
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-7062894;