rs2072035

Positions:

• chr1-175160810-C-G
• chr1-175160810-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014656.3(KIAA0040):​c.204G>C​(p.Lys68Asn) 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. 10/14 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: 25)
• Consequence: KIAA0040 NM_014656.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.514

Genes affected

KIAA0040 (HGNC:28950): (KIAA0040) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14210856).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0040	NM_014656.3	c.204G>C	p.Lys68Asn	missense_variant	4/4	ENST00000423313.6	NP_055471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0040	ENST00000423313.6	c.204G>C	p.Lys68Asn	missense_variant	4/4	1	NM_014656.3	ENSP00000462172.1
KIAA0040	ENST00000444639.5	c.204G>C	p.Lys68Asn	missense_variant	4/4	1		ENSP00000463734.1
KIAA0040	ENST00000545251.6	c.204G>C	p.Lys68Asn	missense_variant	3/3	1		ENSP00000464040.1
KIAA0040	ENST00000619513.1	c.-180G>C		5_prime_UTR_variant	2/2	2		ENSP00000478803.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.2
DANN	Benign	0.89
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.46	.;.;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.14	T;T;T
PrimateAI	Benign	0.46	T
Sift4G	Uncertain	0.046	D;D;D
Vest4		0.22
MVP		0.061
GERP RS		3.0
Varity_R		0.094
gMVP		0.031

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: rs2072035; hg19: chr1-175129946;