NM_001129898.2:c.155C>G

Variant names:

• chrX-46463210-C-G
• rs199723291
• NM_001129898.2:c.155C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001129898.2(KRABD4):​c.155C>G​(p.Ala52Gly) 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. 15/21 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. A52V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000073 (0 hom. 3 hem.)
  • Failed GnomAD Quality Control
• Consequence: KRABD4 NM_001129898.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.090720505).

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.155C>G	p.Ala52Gly	missense	Exon 5 of 6	NP_001123370.1	Q5JUW0-1
	KRABD4	NM_017776.3		c.155C>G	p.Ala52Gly	missense	Exon 5 of 6	NP_060246.2	Q5JUW0-2
	KRABD4	NM_001129899.2		c.155C>G	p.Ala52Gly	missense	Exon 5 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.155C>G	p.Ala52Gly	missense	Exon 5 of 6	ENSP00000345797.4	Q5JUW0-1
	KRBOX4	ENST00000487081.1	TSL:1	c.155C>G	p.Ala52Gly	missense	Exon 4 of 6	ENSP00000418076.1	Q5JUW0-3
	KRBOX4	ENST00000942305.1		c.194C>G	p.Ala65Gly	missense	Exon 5 of 6	ENSP00000612364.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000109 AC: 2 AN: 183299 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000722

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000729 AC: 8 AN: 1097528 Hom.: 0 Cov.: 30 AF XY: 0.00000827 AC XY: 3 AN XY: 362894

African (AFR) AF: 0.00 AC: 0 AN: 26392

American (AMR) AF: 0.0000568 AC: 2 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19377

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30200

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54123

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.00000357 AC: 3 AN: 841504

Other (OTH) AF: 0.0000217 AC: 1 AN: 46064

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.92
DEOGEN2	Benign	0.034	T
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.0087	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.72	N
PhyloP100		-0.32
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.0070
Sift	Benign	0.24	T
Sift4G	Benign	0.14	T
Polyphen		0.0030	B
Vest4		0.12
MutPred		0.36		Loss of ubiquitination at K53 (P = 0.1278)
MVP		0.22
MPC		0.45
ClinPred		0.0085	T
GERP RS		0.38
Varity_R		0.087
gMVP		0.073
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs199723291; hg19: chrX-46322645;