chr18-74446710-G-C

Position:

• chr18-74446710-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001044369.3(DIPK1C):​c.772C>G​(p.Leu258Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: DIPK1C NM_001044369.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.26

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38645995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIPK1C	NM_001044369.3	c.772C>G	p.Leu258Val	missense_variant	2/4	ENST00000343998.8	NP_001037834.2
DIPK1C	XM_047437299.1	c.772C>G	p.Leu258Val	missense_variant	2/3		XP_047293255.1
DIPK1C	XM_017025551.3	c.349C>G	p.Leu117Val	missense_variant	2/4		XP_016881040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIPK1C	ENST00000343998.8	c.772C>G	p.Leu258Val	missense_variant	2/4	5	NM_001044369.3	ENSP00000344331.6
DIPK1C	ENST00000400291.2	c.-21-4594C>G		intron_variant		1		ENSP00000383148.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2022

The c.772C>G (p.L258V) alteration is located in exon 2 (coding exon 2) of the FAM69C gene. This alteration results from a C to G substitution at nucleotide position 772, causing the leucine (L) at amino acid position 258 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Benign	0.043
Eigen_PC	Benign	0.096
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.95	T
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.093
Sift	Benign	0.32	T
Sift4G	Benign	0.089	T
Vest4		0.53
MutPred		0.57		Loss of catalytic residue at L258 (P = 0.1221);
MVP		0.32
MPC		0.37
ClinPred		0.95	D
GERP RS		4.5
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-72113945;