14-37746207-G-T

Variant names:

• chr14-37746207-G-T
• rs1957577
• NM_001310135.5:c.2364-2732G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001310135.5(TTC6):​c.2364-2732G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.935 in 152,170 control chromosomes in the GnomAD database, including 67,305 homozygotes. 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: 𝑓 0.94 (67305 hom., cov: 30)
• Consequence: TTC6 NM_001310135.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.817
• Publications: 2 publications found

Genes affected

TTC6 (HGNC:19739): (tetratricopeptide repeat domain 6)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC6	NM_001310135.5	c.2364-2732G>T		intron_variant	Intron 12 of 32	ENST00000553443.6	NP_001297064.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC6	ENST00000553443.6	c.2364-2732G>T		intron_variant	Intron 12 of 32	5	NM_001310135.5	ENSP00000451131.1
TTC6	ENST00000533625.5	n.*1062+7052G>T		intron_variant	Intron 11 of 18	2		ENSP00000451566.1

Frequencies

GnomAD3 genomes AF: 0.935 AC: 142206 AN: 152052 Hom.: 67270 Cov.: 30

Gnomad AFR AF: 0.777

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.947

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.935 AC: 142300 AN: 152170 Hom.: 67305 Cov.: 30 AF XY: 0.939 AC XY: 69838 AN XY: 74408

African (AFR) AF: 0.777 AC: 32197 AN: 41450

American (AMR) AF: 0.974 AC: 14896 AN: 15298

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5158 AN: 5158

South Asian (SAS) AF: 0.999 AC: 4824 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10620 AN: 10620

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67933 AN: 68026

Other (OTH) AF: 0.948 AC: 2002 AN: 2112

Alfa AF: 0.963 Hom.: 20522

Bravo AF: 0.924

Asia WGS AF: 0.985 AC: 3424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.54
DANN	Benign	0.66
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

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: rs1957577; hg19: chr14-38215412;