chrX-45191837-T-A

Variant names:

• chrX-45191837-T-A
• rs1186455181
• NM_176819.4:c.412A>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_176819.4(DIPK2B):​c.412A>T​(p.Thr138Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000024 in 1,210,468 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., 8 hem., cov: 24)
  • Exomes 𝑓: 0.000013 (0 hom. 1 hem.)
• Consequence: DIPK2B NM_176819.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39
• Publications: 0 publications found

Genes affected

DIPK2B (HGNC:25866): (divergent protein kinase domain 2B) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000229491 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03919944).
• BS2: High Hemizygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIPK2B	NM_176819.4	c.412A>T	p.Thr138Ser	missense_variant	Exon 2 of 5	ENST00000398000.7	NP_789789.2
DIPK2B	NM_024689.3	c.412A>T	p.Thr138Ser	missense_variant	Exon 2 of 3		NP_078965.2
DIPK2B	XM_005272670.1	c.412A>T	p.Thr138Ser	missense_variant	Exon 2 of 4		XP_005272727.1
DIPK2B	XM_006724559.1	c.412A>T	p.Thr138Ser	missense_variant	Exon 2 of 4		XP_006724622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIPK2B	ENST00000398000.7	c.412A>T	p.Thr138Ser	missense_variant	Exon 2 of 5	5	NM_176819.4	ENSP00000381086.2

Frequencies

GnomAD3 genomes AF: 0.000133 AC: 15 AN: 112363 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000491 AC: 9 AN: 183319 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000328

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000127 AC: 14 AN: 1098105 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 1 AN XY: 363459

African (AFR) AF: 0.0000757 AC: 2 AN: 26403

American (AMR) AF: 0.000341 AC: 12 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40518

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842009

Other (OTH) AF: 0.00 AC: 0 AN: 46096

GnomAD4 genome AF: 0.000133 AC: 15 AN: 112363 Hom.: 0 Cov.: 24 AF XY: 0.000232 AC XY: 8 AN XY: 34541

African (AFR) AF: 0.0000324 AC: 1 AN: 30889

American (AMR) AF: 0.00131 AC: 14 AN: 10672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3577

South Asian (SAS) AF: 0.00 AC: 0 AN: 2703

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6181

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53251

Other (OTH) AF: 0.00 AC: 0 AN: 1513

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000159

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 11, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.412A>T (p.T138S) alteration is located in exon 2 (coding exon 2) of the CXorf36 gene. This alteration results from a A to T substitution at nucleotide position 412, causing the threonine (T) at amino acid position 138 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.93
CADD	Benign	10
DANN	Benign	0.83
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.039	T;T
MetaSVM	Benign	-0.99	T
PhyloP100		1.4
PROVEAN	Benign	-0.22	N;N
REVEL	Benign	0.14
Sift	Benign	0.88	T;T
Sift4G	Benign	0.73	T;T
Vest4		0.051
MutPred		0.19		Gain of disorder (P = 0.0236);Gain of disorder (P = 0.0236);
MVP		0.67
MPC		0.21
ClinPred		0.026	T
GERP RS		4.5
gMVP		0.37
Mutation Taster		=98/2	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: rs1186455181; hg19: chrX-45051082;