rs752322173

Variant names:

• chr14-90578174-C-G
• rs752322173
• NM_001010854.2:c.2242G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-90578174-C-G
• chr14-90578174-C-T

Variant summary

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

The NM_001010854.2(TTC7B):​c.2242G>C​(p.Glu748Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,508 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TTC7B NM_001010854.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.84

Genes affected

TTC7B (HGNC:19858): (tetratricopeptide repeat domain 7B) Involved in phosphatidylinositol phosphate biosynthetic process and protein localization to plasma membrane. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC7B	NM_001010854.2	c.2242G>C	p.Glu748Gln	missense_variant	Exon 19 of 20	ENST00000328459.11	NP_001010854.1
TTC7B	NM_001401365.1	c.2455G>C	p.Glu819Gln	missense_variant	Exon 21 of 22		NP_001388294.1
TTC7B	NM_001320421.2	c.1987G>C	p.Glu663Gln	missense_variant	Exon 20 of 21		NP_001307350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC7B	ENST00000328459.11	c.2242G>C	p.Glu748Gln	missense_variant	Exon 19 of 20	1	NM_001010854.2	ENSP00000336127.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249866 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135206

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461508 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727014

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Uncertain	0.20	D
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.1	N;D
REVEL	Uncertain	0.32
Sift	Benign	0.046	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.82	P;.
Vest4		0.79
MutPred		0.53		Gain of MoRF binding (P = 0.0202);.;
MVP		0.25
MPC		0.91
ClinPred		0.88	D
GERP RS		5.5
Varity_R		0.56
gMVP		0.56

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: rs752322173; hg19: chr14-91044518;