NM_152421.4:c.286T>C

Variant names:

• chr9-136722008-T-C
• rs759909032
• NM_152421.4:c.286T>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_152421.4(DIPK1B):​c.286T>C​(p.Ser96Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,612,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: DIPK1B NM_152421.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.16
• 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]

LOC124900276 (HGNC:):

SNHG7 (HGNC:28254): (small nucleolar RNA host gene 7)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.943

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.286T>C	p.Ser96Pro	missense	Exon 3 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.286T>C	p.Ser96Pro	missense	Exon 3 of 5	ENSP00000360757.4	Q5VUD6-1
	DIPK1B	ENST00000371691.5	TSL:1	c.25T>C	p.Ser9Pro	missense	Exon 1 of 3	ENSP00000360756.1	Q5VUD6-2
	DIPK1B	ENST00000931511.1		c.286T>C	p.Ser96Pro	missense	Exon 3 of 5	ENSP00000601570.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151836 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000801 AC: 2 AN: 249664 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1461128 Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7 AN XY: 726866

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111954

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151836 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74160

African (AFR) AF: 0.00 AC: 0 AN: 41290

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67956

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	22
DANN	Uncertain	0.99
Eigen	Benign	0.18
Eigen_PC	Benign	0.089
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.68	T
M_CAP	Pathogenic	0.42	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-0.68	T
PhyloP100		4.2
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0050	D
Vest4		0.83
MutPred		0.72		Gain of relative solvent accessibility (P = 0.1571)
MVP		0.74
MPC		0.18
ClinPred		0.68	D
GERP RS		4.3
gMVP		0.90
Mutation Taster		=50/50

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: rs759909032; hg19: chr9-139616460;