14-20295809-A-G

Position:

• chr14-20295809-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_138376.3(TTC5):​c.742T>C​(p.Ser248Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TTC5 NM_138376.3 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.69

Genes affected

TTC5 (HGNC:19274): (tetratricopeptide repeat domain 5) Predicted to enable DNA binding activity and chromatin binding activity. Predicted to be involved in DNA repair. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TTC5 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 14-20295809-A-G is Pathogenic according to our data. Variant chr14-20295809-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3391116.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC5	NM_138376.3	c.742T>C	p.Ser248Pro	missense_variant	7/10	ENST00000258821.8	NP_612385.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC5	ENST00000258821.8	c.742T>C	p.Ser248Pro	missense_variant	7/10	1	NM_138376.3	ENSP00000258821.3
TTC5	ENST00000383029.7	n.*287T>C		non_coding_transcript_exon_variant	7/10	1		ENSP00000372496.3
TTC5	ENST00000383029.7	n.*287T>C		3_prime_UTR_variant	7/10	1		ENSP00000372496.3
TTC5	ENST00000554157.5	n.753T>C		non_coding_transcript_exon_variant	7/9	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Dec 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.080
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.45
Sift	Benign	0.047	D
Sift4G	Benign	0.088	T
Polyphen		0.54	P
Vest4		0.69
MutPred		0.36		Loss of phosphorylation at S248 (P = 0.0365);
MVP		0.68
MPC		0.35
ClinPred		0.92	D
GERP RS		3.6
Varity_R		0.54
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-20763968;