14-90644157-C-G

Variant names:

• chr14-90644157-C-G
• rs763661174
• NM_001010854.2:c.1642G>C

Variant summary

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

The NM_001010854.2(TTC7B):​c.1642G>C​(p.Asp548His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. D548N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TTC7B NM_001010854.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57
• Publications: 1 publications found

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]

TTC7B-AS1 (HGNC:56196): (TTC7B antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010854.2. 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
	TTC7B	NM_001010854.2	MANE Select	c.1642G>C	p.Asp548His	missense	Exon 15 of 20	NP_001010854.1	Q86TV6-1
	TTC7B	NM_001401365.1		c.1642G>C	p.Asp548His	missense	Exon 15 of 22	NP_001388294.1
	TTC7B	NM_001320421.2		c.1336G>C	p.Asp446His	missense	Exon 15 of 21	NP_001307350.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC7B	ENST00000328459.11	TSL:1 MANE Select	c.1642G>C	p.Asp548His	missense	Exon 15 of 20	ENSP00000336127.4	Q86TV6-1
	TTC7B	ENST00000553972.5	TSL:1	c.52G>C	p.Asp18His	missense	Exon 1 of 7	ENSP00000451440.1	A0A0C4DGK5
	TTC7B-AS1	ENST00000557007.1	TSL:1	n.92-587C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	0.064	D
MutationAssessor	Benign	1.2	L
PhyloP100		7.6
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.79	N
REVEL	Uncertain	0.41
Sift	Benign	0.36	T
Sift4G	Benign	0.33	T
Polyphen		1.0	D
Vest4		0.84
MutPred		0.44		Gain of catalytic residue at Q545 (P = 0.0657)
MVP		0.58
MPC		1.2
ClinPred		0.93	D
GERP RS		5.8
PromoterAI		-0.051	Neutral
Varity_R		0.33
gMVP		0.58
Mutation Taster		=32/68	disease causing

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: rs763661174; hg19: chr14-91110501;