X-46472847-T-C

Variant names:

• chrX-46472847-T-C
• rs373750614
• NM_001129898.2:c.351T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001129898.2(KRABD4):​c.351T>C​(p.Asp117Asp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: KRABD4 NM_001129898.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.822
• Publications: 0 publications found

Genes affected

KRABD4 (HGNC:26007): (KRAB box domain containing 4) This encodes a zinc finger protein with an N-terminal KRAB (Kruppel-associated) domain found in transcriptional repressors. This gene is located in a region of the X chromosome thought to be involved in nonsyndromic X-linked cognitive disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=0.822 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001129898.2. 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
	KRABD4	NM_001129898.2	MANE Select	c.351T>C	p.Asp117Asp	synonymous	Exon 6 of 6	NP_001123370.1	Q5JUW0-1
	KRABD4	NM_017776.3		c.336T>C	p.Asp112Asp	synonymous	Exon 6 of 6	NP_060246.2	Q5JUW0-2
	KRABD4	NM_001129899.2		c.*98T>C		3_prime_UTR	Exon 7 of 7	NP_001123371.1	Q5JUW0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRBOX4	ENST00000344302.9	TSL:2 MANE Select	c.351T>C	p.Asp117Asp	synonymous	Exon 6 of 6	ENSP00000345797.4	Q5JUW0-1
	KRBOX4	ENST00000487081.1	TSL:1	c.*95T>C		3_prime_UTR	Exon 6 of 6	ENSP00000418076.1	Q5JUW0-3
	KRBOX4	ENST00000942305.1		c.375T>C	p.Asp125Asp	synonymous	Exon 6 of 6	ENSP00000612364.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.11e-7 AC: 1 AN: 1098186 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363546

African (AFR) AF: 0.0000379 AC: 1 AN: 26401

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30202

South Asian (SAS) AF: 0.00 AC: 0 AN: 54145

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842086

Other (OTH) AF: 0.00 AC: 0 AN: 46093

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
DANN	Benign	0.49
PhyloP100		0.82

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: rs373750614; hg19: chrX-46332282;