9-136722290-A-G

Position:

• chr9-136722290-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152421.4(DIPK1B):​c.472A>G​(p.Ser158Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 1,612,702 control chromosomes in the GnomAD database, including 715,682 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.86 (58327 hom., cov: 32)
  • Exomes 𝑓: 0.95 (657355 hom.)
• Consequence: DIPK1B NM_152421.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.469048E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIPK1B	NM_152421.4	c.472A>G	p.Ser158Gly	missense_variant	4/5	ENST00000371692.9	NP_689634.2
LOC124900276	XM_047424334.1	c.-2015T>C		5_prime_UTR_variant	5/5		XP_047280290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIPK1B	ENST00000371692.9	c.472A>G	p.Ser158Gly	missense_variant	4/5	1	NM_152421.4	ENSP00000360757.4
DIPK1B	ENST00000371691.5	c.211A>G	p.Ser71Gly	missense_variant	2/3	1		ENSP00000360756.1
SNHG7	ENST00000414282.5	n.1433T>C		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.862 AC: 131003 AN: 152018 Hom.: 58310 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.939

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.976

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.959

Gnomad OTH AF: 0.882

GnomAD3 exomes AF: 0.930 AC: 230537 AN: 247844 Hom.: 108318 AF XY: 0.933 AC XY: 125310 AN XY: 134376

Gnomad AFR exome AF: 0.606

Gnomad AMR exome AF: 0.965

Gnomad ASJ exome AF: 0.943

Gnomad EAS exome AF: 0.999

Gnomad SAS exome AF: 0.872

Gnomad FIN exome AF: 0.974

Gnomad NFE exome AF: 0.960

Gnomad OTH exome AF: 0.940

GnomAD4 exome AF: 0.947 AC: 1382792 AN: 1460566 Hom.: 657355 Cov.: 67 AF XY: 0.945 AC XY: 686882 AN XY: 726526

Gnomad4 AFR exome AF: 0.603

Gnomad4 AMR exome AF: 0.963

Gnomad4 ASJ exome AF: 0.941

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.871

Gnomad4 FIN exome AF: 0.974

Gnomad4 NFE exome AF: 0.960

Gnomad4 OTH exome AF: 0.929

GnomAD4 genome AF: 0.862 AC: 131067 AN: 152136 Hom.: 58327 Cov.: 32 AF XY: 0.866 AC XY: 64420 AN XY: 74370

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.936

Gnomad4 ASJ AF: 0.939

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.873

Gnomad4 FIN AF: 0.976

Gnomad4 NFE AF: 0.959

Gnomad4 OTH AF: 0.883

Alfa AF: 0.939 Hom.: 95779

Bravo AF: 0.852

TwinsUK AF: 0.958 AC: 3554

ALSPAC AF: 0.963 AC: 3711

ESP6500AA AF: 0.621 AC: 2735

ESP6500EA AF: 0.958 AC: 8242

ExAC AF: 0.921 AC: 111698

Asia WGS AF: 0.919 AC: 3197 AN: 3478

EpiCase AF: 0.954

EpiControl AF: 0.952

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Uncertain	0.99
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.66	T;T
MetaRNN	Benign	5.5e-7	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.067
Sift	Benign	0.20	T;T
Sift4G	Benign	0.11	T;T
Vest4		0.048
MPC		0.12
ClinPred		0.0034	T
GERP RS		0.85
gMVP		0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs945384; hg19: chr9-139616742;