5-95656094-A-G

Position:

• chr5-95656094-A-G

Variant summary

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

The NM_001131066.2(RFESD):​c.418A>G​(p.Ile140Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RFESD NM_001131066.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.46

Genes affected

RFESD (HGNC:29587): (Rieske Fe-S domain containing) Predicted to enable 2 iron, 2 sulfur cluster binding activity and metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

SPATA9 (HGNC:22988): (spermatogenesis associated 9) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPATA9 (HGNC:):

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/exons	MANE	Protein	UniProt
RFESD	NM_001131066.2	c.418A>G	p.Ile140Val	missense_variant	6/6	ENST00000380005.9	NP_001124538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFESD	ENST00000380005.9	c.418A>G	p.Ile140Val	missense_variant	6/6	2	NM_001131066.2	ENSP00000369341.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 15, 2024

The c.418A>G (p.I140V) alteration is located in exon 6 (coding exon 5) of the RFESD gene. This alteration results from a A to G substitution at nucleotide position 418, causing the isoleucine (I) at amino acid position 140 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	0.32
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T;.;T;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D;.;D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.65	D;D;D;D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Uncertain	2.3	.;.;M;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.86	N;N;N;N
REVEL	Uncertain	0.45
Sift	Uncertain	0.010	D;T;D;T
Sift4G	Uncertain	0.014	D;D;D;D
Polyphen		0.99	D;.;D;.
Vest4		0.43, 0.46, 0.44
MutPred		0.64		Gain of catalytic residue at I87 (P = 0.0026);.;Gain of catalytic residue at I87 (P = 0.0026);.;
MVP		0.081
MPC		0.54
ClinPred		0.86	D
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.55

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: chr5-94991798;