rs201065562

Variant names:

• chr16-1510952-C-G
• rs201065562
• NM_014714.4:c.4381G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-1510952-C-G
• chr16-1510952-C-T

Variant summary

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

The NM_014714.4(IFT140):​c.4381G>C​(p.Asp1461His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. D1461N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: IFT140 NM_014714.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

Genes affected

IFT140 (HGNC:29077): (intraflagellar transport 140) This gene encodes one of the subunits of the intraflagellar transport (IFT) complex A. Intraflagellar transport is involved in the genesis, resorption and signaling of primary cilia. The primary cilium is a microtubule-based sensory organelle at the surface of most quiescent mammalian cells, that receives signals from its environment, such as the flow of fluid, light or odors, and transduces those signals to the nucleus. Loss of the corresponding protein in mouse results in renal cystic disease. [provided by RefSeq, Jun 2012]

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=0.1583862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT140	NM_014714.4	c.4381G>C	p.Asp1461His	missense_variant	Exon 31 of 31	ENST00000426508.7	NP_055529.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT140	ENST00000426508.7	c.4381G>C	p.Asp1461His	missense_variant	Exon 31 of 31	5	NM_014714.4	ENSP00000406012.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458942 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725578

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.84
DEOGEN2	Benign	0.0095	.;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.3	.;M
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.13
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.023	D;D
Polyphen		0.93	.;P
Vest4		0.15
MutPred		0.17		.;Loss of solvent accessibility (P = 0.0217);
MVP		0.51
MPC		0.079
ClinPred		0.22	T
GERP RS		2.6
Varity_R		0.053
gMVP		0.25

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: rs201065562; hg19: chr16-1560953;