rs370634407

Variant names:

• chr8-144881712-C-A
• rs370634407
• NM_001109689.4:c.1471G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-144881712-C-A
• chr8-144881712-C-T

Variant summary

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

The NM_001109689.4(ZNF250):​c.1471G>T​(p.Val491Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 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. V491M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ZNF250 NM_001109689.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529
• Publications: 0 publications found

Genes affected

ZNF250 (HGNC:13044): (zinc finger protein 250) Enables identical protein binding activity and sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [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=0.06535733).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001109689.4. 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
	ZNF250	NM_001109689.4	MANE Select	c.1471G>T	p.Val491Leu	missense	Exon 6 of 6	NP_001103159.1	P15622-3
	ZNF250	NM_001363098.2		c.1486G>T	p.Val496Leu	missense	Exon 6 of 6	NP_001350027.1	P15622-1
	ZNF250	NM_001363099.2		c.1486G>T	p.Val496Leu	missense	Exon 6 of 6	NP_001350028.1	P15622-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF250	ENST00000417550.7	TSL:1 MANE Select	c.1471G>T	p.Val491Leu	missense	Exon 6 of 6	ENSP00000393442.2	P15622-3
	ZNF250	ENST00000292579.11	TSL:1	c.1486G>T	p.Val496Leu	missense	Exon 6 of 6	ENSP00000292579.7	P15622-1
	ZNF250	ENST00000940320.1		c.1489G>T	p.Val497Leu	missense	Exon 6 of 6	ENSP00000610379.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461754 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727164

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111934

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Benign	0.44
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.36	N
PhyloP100		-0.53
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.11
Sift	Benign	0.39	T
Sift4G	Benign	0.59	T
Polyphen		0.018	B
Vest4		0.15
MutPred		0.32		Gain of loop (P = 0.1069)
MVP		0.32
MPC		0.46
ClinPred		0.37	T
GERP RS		4.0
Varity_R		0.11
gMVP		0.17
Mutation Taster		=90/10	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: rs370634407; hg19: chr8-146107097;