chr5-95656197-C-T

Variant names:

• chr5-95656197-C-T
• NM_001131066.2:c.521C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001131066.2(RFESD):​c.521C>T​(p.Thr174Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 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: -2.83
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06496245).

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.521C>T	p.Thr174Ile	missense	Exon 6 of 6	NP_001124538.1	Q8TAC1-2
	RFESD	NM_001131065.1		c.521C>T	p.Thr174Ile	missense	Exon 6 of 6	NP_001124537.1	Q8TAC1-2
	RFESD	NM_001375394.1		c.362C>T	p.Thr121Ile	missense	Exon 5 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.521C>T	p.Thr174Ile	missense	Exon 6 of 6	ENSP00000369341.4	Q8TAC1-2
	RFESD	ENST00000311364.9	TSL:1	c.362C>T	p.Thr121Ile	missense	Exon 5 of 5	ENSP00000309229.4	Q8TAC1-1
	SPATA9	ENST00000316087.12	TSL:1	n.*154-120G>A		intron	N/A	ENSP00000325491.8	Q9BWV2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Benign	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.9
DANN	Benign	0.91
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-2.8
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.029
Sift	Benign	0.17	T
Sift4G	Benign	0.11	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.49		Gain of sheet (P = 0.0344)
MVP		0.014
MPC		0.14
ClinPred		0.11	T
GERP RS		-4.5
Varity_R		0.056
gMVP		0.43
Mutation Taster		=88/12	polymorphism

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

hg19: chr5-94991901;