9-136712709-C-A

Variant names:

• chr9-136712709-C-A
• rs1214132520
• NM_152421.4:c.44C>A

Variant summary

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

The NM_152421.4(DIPK1B):​c.44C>A​(p.Pro15His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000822 in 1,217,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P15R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: DIPK1B NM_152421.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.676
• 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=0.26760995).

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.44C>A	p.Pro15His	missense	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.44C>A	p.Pro15His	missense	Exon 1 of 5	ENSP00000360757.4	Q5VUD6-1
	DIPK1B	ENST00000931511.1		c.44C>A	p.Pro15His	missense	Exon 1 of 5	ENSP00000601570.1
	DIPK1B	ENST00000931512.1		c.44C>A	p.Pro15His	missense	Exon 1 of 5	ENSP00000601571.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.22e-7 AC: 1 AN: 1217108 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 597344

African (AFR) AF: 0.00 AC: 0 AN: 24370

American (AMR) AF: 0.00 AC: 0 AN: 15338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19328

East Asian (EAS) AF: 0.00 AC: 0 AN: 27342

South Asian (SAS) AF: 0.00 AC: 0 AN: 55276

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3400

European-Non Finnish (NFE) AF: 0.00000101 AC: 1 AN: 994484

Other (OTH) AF: 0.00 AC: 0 AN: 49148

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	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.071
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.87	T
PhyloP100		0.68
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Vest4		0.24
MutPred		0.53		Loss of sheet (P = 0.0315)
MVP		0.66
MPC		0.53
ClinPred		0.88	D
GERP RS		2.2
PromoterAI		-0.061	Neutral
gMVP		0.76
Mutation Taster		=80/20	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: rs1214132520; hg19: chr9-139607161;