1-178520430-A-C

Variant names:

• chr1-178520430-A-C
• rs746740772
• NM_032126.5:c.335A>C

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.335A>C​(p.Tyr112Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. Y112C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TEX35 NM_032126.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• 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=0.05835405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX35	NM_032126.5	c.335A>C	p.Tyr112Ser	missense_variant	Exon 6 of 9	ENST00000319416.7	NP_115502.2
TEX35	NM_001170722.2	c.359A>C	p.Tyr120Ser	missense_variant	Exon 6 of 9		NP_001164193.1
TEX35	NM_001170723.2	c.335A>C	p.Tyr112Ser	missense_variant	Exon 6 of 9		NP_001164194.1
TEX35	NM_001170724.2	c.335A>C	p.Tyr112Ser	missense_variant	Exon 6 of 9		NP_001164195.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX35	ENST00000319416.7	c.335A>C	p.Tyr112Ser	missense_variant	Exon 6 of 9	1	NM_032126.5	ENSP00000323795.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.2
DANN	Benign	0.65
DEOGEN2	Benign	0.0020	T;.;.;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.46	T;T;T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.058	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.69	N;N;N;.
PhyloP100		1.1
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.6	N;N;N;N
REVEL	Benign	0.037
Sift	Benign	0.55	T;T;T;T
Sift4G	Benign	0.59	T;T;T;T
Polyphen		0.0	B;.;B;B
Vest4		0.19
MutPred		0.16		Loss of stability (P = 0.0375);Loss of stability (P = 0.0375);Loss of stability (P = 0.0375);.;
MVP		0.17
MPC		0.13
ClinPred		0.15	T
GERP RS		2.3
PromoterAI		-0.013	Neutral
Varity_R		0.049
gMVP		0.0070
Mutation Taster		=95/5	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: rs746740772; hg19: chr1-178489565;