X-46499906-T-C

Position:

• chrX-46499906-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001190417.2(ZNF674):​c.1668A>G​(p.Ala556=) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ZNF674 NM_001190417.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.08

Genes affected

ZNF674 (HGNC:17625): (zinc finger protein 674) This gene encodes a zinc finger protein with an N-terminal Kruppel-associated box-containing (KRAB) domain and 11 Kruppel-type C2H2 zinc finger domains. Like other zinc finger proteins, this gene may function as a transcription factor. This gene resides on an area of chromosome X that has been implicated in nonsyndromic X-linked cognitive disabilities. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant X-46499906-T-C is Benign according to our data. Variant chrX-46499906-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2660379.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.08 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF674	NM_001190417.2	c.1668A>G	p.Ala556=	synonymous_variant	6/6	ENST00000683375.1	NP_001177346.1
ZNF674	NM_001039891.3	c.1683A>G	p.Ala561=	synonymous_variant	6/6		NP_001034980.1
ZNF674	NM_001146291.2	c.1665A>G	p.Ala555=	synonymous_variant	6/6		NP_001139763.1
ZNF674	XM_011543943.4	c.1680A>G	p.Ala560=	synonymous_variant	6/6		XP_011542245.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF674	ENST00000683375.1	c.1668A>G	p.Ala556=	synonymous_variant	6/6		NM_001190417.2	ENSP00000506769	A1
ZNF674	ENST00000523374.5	c.1683A>G	p.Ala561=	synonymous_variant	6/6	1		ENSP00000429148	P4
ZNF674	ENST00000414387.6	c.1665A>G	p.Ala555=	synonymous_variant	5/5	3		ENSP00000428248	A1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

ZNF674: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.72

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: chrX-46359341;