rs1365210148

Variant names:

• chr2-101412995-C-G
• rs1365210148
• NM_001145664.2:c.638G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-101412995-C-G
• chr2-101412995-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001145664.2(RFX8):​c.638G>C​(p.Gly213Ala) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RFX8 NM_001145664.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.143
• Publications: 0 publications found

Genes affected

RFX8 (HGNC:37253): (regulatory factor X8) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047392637).
• BP6: Variant 2-101412995-C-G is Benign according to our data. Variant chr2-101412995-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2495377.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145664.2. 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
	RFX8	NM_001145664.2	MANE Select	c.638G>C	p.Gly213Ala	missense	Exon 8 of 12	NP_001139136.2	Q6ZV50-3
	RFX8	NM_001367508.1		c.125G>C	p.Gly42Ala	missense	Exon 9 of 13	NP_001354437.1
	RFX8	NM_001367509.1		c.125G>C	p.Gly42Ala	missense	Exon 10 of 14	NP_001354438.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFX8	ENST00000428343.6	TSL:2 MANE Select	c.638G>C	p.Gly213Ala	missense	Exon 8 of 12	ENSP00000401536.1	Q6ZV50-3
	RFX8	ENST00000646893.2		c.977G>C	p.Gly326Ala	missense	Exon 11 of 15	ENSP00000494249.2	Q6ZV50-1
	RFX8	ENST00000646446.1		c.851G>C	p.Gly284Ala	missense	Exon 11 of 15	ENSP00000494216.1	A0A2R8Y560

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.13
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.46
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.14
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.051
Sift	Benign	0.25	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0040	B
Vest4		0.086
MVP		0.014
MPC		0.00045
ClinPred		0.10	T
GERP RS		1.5
gMVP		0.063
Mutation Taster		=94/6	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

dbSNP: rs1365210148; hg19: chr2-102029457;