9-136722290-A-G

Variant names:

• chr9-136722290-A-G
• rs945384
• NM_152421.4:c.472A>G

Variant summary

Our verdict is Benign. The variant received -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. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 24 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]

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

LOC124900276 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DIPK1B	NM_152421.4	c.472A>G	p.Ser158Gly	missense_variant	Exon 4 of 5	ENST00000371692.9	NP_689634.2
LOC124900276	XM_047424334.1	c.-2015T>C		5_prime_UTR_variant	Exon 5 of 5		XP_047280290.1

Ensembl

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

GnomAD2 exomes AF: 0.930 AC: 230537 AN: 247844 AF XY: 0.933

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 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

African (AFR) AF: 0.603 AC: 20177 AN: 33460

American (AMR) AF: 0.963 AC: 42915 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 24564 AN: 26094

East Asian (EAS) AF: 0.999 AC: 39663 AN: 39686

South Asian (SAS) AF: 0.871 AC: 74985 AN: 86098

European-Finnish (FIN) AF: 0.974 AC: 51647 AN: 53038

Middle Eastern (MID) AF: 0.909 AC: 5235 AN: 5760

European-Non Finnish (NFE) AF: 0.960 AC: 1067519 AN: 1111510

Other (OTH) AF: 0.929 AC: 56087 AN: 60344

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

African (AFR) AF: 0.615 AC: 25518 AN: 41478

American (AMR) AF: 0.936 AC: 14314 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.939 AC: 3259 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5150 AN: 5158

South Asian (SAS) AF: 0.873 AC: 4209 AN: 4824

European-Finnish (FIN) AF: 0.976 AC: 10375 AN: 10626

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.959 AC: 65203 AN: 67962

Other (OTH) AF: 0.883 AC: 1865 AN: 2112

Alfa AF: 0.923 Hom.: 127104

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
PhyloP100		1.6
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
Mutation Taster		=96/4	polymorphism (auto)

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: rs945384; hg19: chr9-139616742; COSMIC: COSV107454539; COSMIC: COSV107454539;