chr6-44282139-T-A

Position:

• chr6-44282139-T-A

Variant summary

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

The NM_182539.4(TCTE1):​c.1267A>T​(p.Ile423Phe) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TCTE1 NM_182539.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.932

Genes affected

TCTE1 (HGNC:11693): (t-complex-associated-testis-expressed 1) Predicted to be involved in flagellated sperm motility. Predicted to be located in sperm flagellum. [provided by Alliance of Genome Resources, Apr 2022]

POLR1C (HGNC:):

TMEM151B (HGNC:21315): (transmembrane protein 151B) Predicted to be integral component of 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/exons	MANE	Protein	UniProt
TCTE1	NM_182539.4	c.1267A>T	p.Ile423Phe	missense_variant	4/5	ENST00000371505.5	NP_872345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCTE1	ENST00000371505.5	c.1267A>T	p.Ile423Phe	missense_variant	4/5	1	NM_182539.4	ENSP00000360560	P1
TCTE1	ENST00000371504.1	c.388-1749A>T		intron_variant		3		ENSP00000360559
TMEM151B	ENST00000438774.2	c.576+8633T>A		intron_variant		3		ENSP00000409337

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 22, 2024

The c.1267A>T (p.I423F) alteration is located in exon 4 (coding exon 3) of the TCTE1 gene. This alteration results from a A to T substitution at nucleotide position 1267, causing the isoleucine (I) at amino acid position 423 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.072
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.020	D
Polyphen		0.97	D
Vest4		0.75
MutPred		0.68		Gain of sheet (P = 0.1208);
MVP		0.30
MPC		1.2
ClinPred		0.97	D
GERP RS		-0.22
Varity_R		0.33
gMVP		0.65

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: chr6-44249876;