NM_014656.3:c.118A>T

Variant names:

• chr1-175160896-T-A
• rs377186715
• NM_014656.3:c.118A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014656.3(KIAA0040):​c.118A>T​(p.Ile40Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I40V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KIAA0040 NM_014656.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.477
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.089650005).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014656.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0040	NM_014656.3	MANE Select	c.118A>T	p.Ile40Phe	missense	Exon 4 of 4	NP_055471.2	Q15053
	KIAA0040	NM_001162893.2		c.118A>T	p.Ile40Phe	missense	Exon 5 of 5	NP_001156365.1	Q15053
	KIAA0040	NM_001162894.2		c.118A>T	p.Ile40Phe	missense	Exon 4 of 4	NP_001156366.1	Q15053

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0040	ENST00000423313.6	TSL:1 MANE Select	c.118A>T	p.Ile40Phe	missense	Exon 4 of 4	ENSP00000462172.1	Q15053
	KIAA0040	ENST00000444639.5	TSL:1	c.118A>T	p.Ile40Phe	missense	Exon 4 of 4	ENSP00000463734.1	Q15053
	KIAA0040	ENST00000545251.6	TSL:1	c.118A>T	p.Ile40Phe	missense	Exon 3 of 3	ENSP00000464040.1	Q15053

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399348 Hom.: 0 Cov.: 35 AF XY: 0.00000145 AC XY: 1 AN XY: 690178

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.0000252 AC: 2 AN: 79230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078968

Other (OTH) AF: 0.00 AC: 0 AN: 57990

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.6
DANN	Benign	0.39
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.090	T
PhyloP100		-0.48
PrimateAI	Benign	0.36	T
Sift4G	Uncertain	0.053	T
Vest4		0.17
MVP		0.030
GERP RS		-11
Varity_R		0.050
gMVP		0.041
Mutation Taster		=91/9	polymorphism

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: rs377186715; hg19: chr1-175130032;