5-95654227-C-A

Variant names:

• chr5-95654227-C-A
• rs764934254
• NM_001131066.2:c.325C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001131066.2(RFESD):​c.325C>A​(p.Arg109Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R109C) has been classified 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: 1.91
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001131066.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFESD	NM_001131066.2	MANE Select	c.325C>A	p.Arg109Ser	missense	Exon 4 of 6	NP_001124538.1	Q8TAC1-2
	RFESD	NM_001131065.1		c.325C>A	p.Arg109Ser	missense	Exon 4 of 6	NP_001124537.1	Q8TAC1-2
	RFESD	NM_001375394.1		c.166C>A	p.Arg56Ser	missense	Exon 3 of 5	NP_001362323.1	Q8TAC1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFESD	ENST00000380005.9	TSL:2 MANE Select	c.325C>A	p.Arg109Ser	missense	Exon 4 of 6	ENSP00000369341.4	Q8TAC1-2
	RFESD	ENST00000311364.9	TSL:1	c.166C>A	p.Arg56Ser	missense	Exon 3 of 5	ENSP00000309229.4	Q8TAC1-1
	SPATA9	ENST00000316087.12	TSL:1	n.*448-1018G>T		intron	N/A	ENSP00000325491.8	Q9BWV2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0046	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.9
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.28
Sift	Benign	0.36	T
Sift4G	Benign	0.36	T
Polyphen		1.0	D
Vest4		0.68
MutPred		0.58		Loss of sheet (P = 0.1158)
MVP		0.23
MPC		0.59
ClinPred		0.96	D
GERP RS		5.7
PromoterAI		-0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.70
gMVP		0.88
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs764934254; hg19: chr5-94989931;