rs375743897

Variant names:

• chr12-110127405-A-C
• NM_014055.4:c.25A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-110127405-A-C
• chr12-110127405-A-G

Variant summary

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

The NM_001347947.2(IFT81):​c.-742A>C variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000139 in 1,443,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IFT81 NM_001347947.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.48

Genes affected

IFT81 (HGNC:14313): (intraflagellar transport 81) The protein encoded by this gene, together with IFT74, forms a tubulin-binding module of intraflagellar transport complex B. This module is involved in transport of tubulin within the cilium, and the encoded protein is required for ciliogenesis. Mutations in this gene are a cause of short-rib polydactyly syndromes. [provided by RefSeq, Dec 2016]

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=0.20306021).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT81	NM_014055.4	c.25A>C	p.Met9Leu	missense_variant	Exon 2 of 19	ENST00000242591.10	NP_054774.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT81	ENST00000242591.10	c.25A>C	p.Met9Leu	missense_variant	Exon 2 of 19	1	NM_014055.4	ENSP00000242591.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1443018 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 717008

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Benign	0.94
DEOGEN2	Benign	0.032	.;T;T;.
Eigen	Benign	-0.24
Eigen_PC	Benign	0.021
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D;.;D;D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	-0.34	N;N;N;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.11	N;N;N;N
REVEL	Benign	0.25
Sift	Uncertain	0.013	D;D;D;D
Sift4G	Uncertain	0.016	D;D;D;D
Polyphen		0.0010	B;B;B;.
Vest4		0.23
MutPred		0.30		Gain of catalytic residue at I5 (P = 0.002);Gain of catalytic residue at I5 (P = 0.002);Gain of catalytic residue at I5 (P = 0.002);Gain of catalytic residue at I5 (P = 0.002);
MVP		0.48
MPC		0.12
ClinPred		0.89	D
GERP RS		5.3
Varity_R		0.16
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr12-110565210;