18-74446688-T-C

Position:

• chr18-74446688-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001044369.3(DIPK1C):​c.794A>G​(p.Asn265Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 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: not found (cov: 34)
• Consequence: DIPK1C NM_001044369.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.301

Genes affected

DIPK1C (HGNC:31729): (divergent protein kinase domain 1C) 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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044715315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIPK1C	NM_001044369.3	c.794A>G	p.Asn265Ser	missense_variant	2/4	ENST00000343998.8	NP_001037834.2
DIPK1C	XM_047437299.1	c.794A>G	p.Asn265Ser	missense_variant	2/3		XP_047293255.1
DIPK1C	XM_017025551.3	c.371A>G	p.Asn124Ser	missense_variant	2/4		XP_016881040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIPK1C	ENST00000343998.8	c.794A>G	p.Asn265Ser	missense_variant	2/4	5	NM_001044369.3	ENSP00000344331.6
DIPK1C	ENST00000400291.2	c.-21-4572A>G		intron_variant		1		ENSP00000383148.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.85
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.029
Sift	Benign	0.75	T
Sift4G	Benign	0.91	T
Vest4		0.019
MutPred		0.32		Gain of disorder (P = 0.0483);
MVP		0.12
MPC		0.069
ClinPred		0.030	T
GERP RS		1.3
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-72113923;