chr9-136712727-A-T

Variant names:

• chr9-136712727-A-T
• rs1200523384
• NM_152421.4:c.62A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152421.4(DIPK1B):​c.62A>T​(p.Gln21Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000167 in 1,198,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. Q21P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: DIPK1B NM_152421.4 missense, splice_region
• Scores: Splicing: ADA: 0.1078
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 0 publications found

Genes affected

DIPK1B (HGNC:28290): (divergent protein kinase domain 1B) This gene encodes a member of the FAM69 family of cysteine-rich type II transmembrane proteins. These proteins localize to the endoplasmic reticulum but their specific functions are unknown. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3042733).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152421.4. 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
	DIPK1B	NM_152421.4	MANE Select	c.62A>T	p.Gln21Leu	missense splice_region	Exon 1 of 5	NP_689634.2	Q5VUD6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIPK1B	ENST00000371692.9	TSL:1 MANE Select	c.62A>T	p.Gln21Leu	missense splice_region	Exon 1 of 5	ENSP00000360757.4	Q5VUD6-1
	DIPK1B	ENST00000931511.1		c.62A>T	p.Gln21Leu	missense splice_region	Exon 1 of 5	ENSP00000601570.1
	DIPK1B	ENST00000931512.1		c.62A>T	p.Gln21Leu	missense splice_region	Exon 1 of 5	ENSP00000601571.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000167 AC: 2 AN: 1198072 Hom.: 0 Cov.: 30 AF XY: 0.00000170 AC XY: 1 AN XY: 586680

African (AFR) AF: 0.00 AC: 0 AN: 23812

American (AMR) AF: 0.00 AC: 0 AN: 12542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18118

East Asian (EAS) AF: 0.00 AC: 0 AN: 27282

South Asian (SAS) AF: 0.00 AC: 0 AN: 50800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3312

European-Non Finnish (NFE) AF: 0.00000203 AC: 2 AN: 986304

Other (OTH) AF: 0.00 AC: 0 AN: 48358

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Benign	0.96
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.66	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.5
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.078
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.076	T
Vest4		0.33
MutPred		0.28		Loss of methylation at K18 (P = 0.0853)
MVP		0.68
MPC		0.24
ClinPred		0.81	D
GERP RS		2.1
PromoterAI		0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.69
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.11
dbscSNV1_RF	Benign	0.44
SpliceAI score (max)		0.14		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: rs1200523384; hg19: chr9-139607179;