1-178520758-A-T

Variant names:

• chr1-178520758-A-T
• rs772030155
• NM_032126.5:c.427A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032126.5(TEX35):​c.427A>T​(p.Met143Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,614,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: TEX35 NM_032126.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0610
• Publications: 0 publications found

Genes affected

TEX35 (HGNC:25366): (testis expressed 35) Located in microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05596021).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX35	NM_032126.5	c.427A>T	p.Met143Leu	missense_variant	Exon 7 of 9	ENST00000319416.7	NP_115502.2
TEX35	NM_001170722.2	c.451A>T	p.Met151Leu	missense_variant	Exon 7 of 9		NP_001164193.1
TEX35	NM_001170723.2	c.427A>T	p.Met143Leu	missense_variant	Exon 7 of 9		NP_001164194.1
TEX35	NM_001170724.2	c.427A>T	p.Met143Leu	missense_variant	Exon 7 of 9		NP_001164195.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX35	ENST00000319416.7	c.427A>T	p.Met143Leu	missense_variant	Exon 7 of 9	1	NM_032126.5	ENSP00000323795.2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152110 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251450 AF XY: 0.0000147

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6 AN XY: 727246

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152110 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74304

African (AFR) AF: 0.00 AC: 0 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000468 Hom.: 0

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 07, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.427A>T (p.M143L) alteration is located in exon 7 (coding exon 7) of the TEX35 gene. This alteration results from a A to T substitution at nucleotide position 427, causing the methionine (M) at amino acid position 143 to be replaced by a leucine (L). 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	0.19
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.7
DANN	Benign	0.47
DEOGEN2	Benign	0.0072	T;.;.;.
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.55	T;T;T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.056	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.46	N;N;N;.
PhyloP100		0.061
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.5	N;N;N;N
REVEL	Benign	0.018
Sift	Benign	0.038	D;D;D;D
Sift4G	Benign	0.36	T;T;T;T
Polyphen		0.0010	B;.;B;B
Vest4		0.14
MutPred		0.22		Loss of MoRF binding (P = 0.0772);Loss of MoRF binding (P = 0.0772);Loss of MoRF binding (P = 0.0772);.;
MVP		0.030
MPC		0.21
ClinPred		0.058	T
GERP RS		-1.3
PromoterAI		-0.049	Neutral
Varity_R		0.22
gMVP		0.0095
Mutation Taster		=100/0	polymorphism

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: rs772030155; hg19: chr1-178489893;