chrX-46501237-C-A

Position:

• chrX-46501237-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001190417.2(ZNF674):​c.337G>T​(p.Glu113Ter) variant causes a stop gained 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 (no stars).

• Frequency: Genomes: not found (cov: 22)
• Consequence: ZNF674 NM_001190417.2 stop_gained
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -2.06

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF674	NM_001190417.2	c.337G>T	p.Glu113Ter	stop_gained	6/6	ENST00000683375.1	NP_001177346.1
ZNF674	NM_001039891.3	c.352G>T	p.Glu118Ter	stop_gained	6/6		NP_001034980.1
ZNF674	NM_001146291.2	c.334G>T	p.Glu112Ter	stop_gained	6/6		NP_001139763.1
ZNF674	XM_011543943.4	c.349G>T	p.Glu117Ter	stop_gained	6/6		XP_011542245.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF674	ENST00000683375.1	c.337G>T	p.Glu113Ter	stop_gained	6/6		NM_001190417.2	ENSP00000506769	A1
ZNF674	ENST00000523374.5	c.352G>T	p.Glu118Ter	stop_gained	6/6	1		ENSP00000429148	P4
ZNF674	ENST00000414387.6	c.334G>T	p.Glu112Ter	stop_gained	5/5	3		ENSP00000428248	A1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Aug 08, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	23
DANN	Uncertain	0.99
FATHMM_MKL	Benign	0.089	N
MutationTaster	Benign	1.0	A;A
Vest4		0.060
GERP RS		-1.3

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

LitVar

Other links and lift over

dbSNP: rs121918362; hg19: chrX-46360672;