1-178520858-A-C

Variant names:

• chr1-178520858-A-C
• rs575322146
• NM_032126.5:c.527A>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.527A>C​(p.His176Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,842 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. 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. H176R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TEX35 NM_032126.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.778
• 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=0.031850725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX35	NM_032126.5	c.527A>C	p.His176Pro	missense_variant	Exon 7 of 9	ENST00000319416.7	NP_115502.2
TEX35	NM_001170722.2	c.551A>C	p.His184Pro	missense_variant	Exon 7 of 9		NP_001164193.1
TEX35	NM_001170723.2	c.527A>C	p.His176Pro	missense_variant	Exon 7 of 9		NP_001164194.1
TEX35	NM_001170724.2	c.527A>C	p.His176Pro	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.527A>C	p.His176Pro	missense_variant	Exon 7 of 9	1	NM_032126.5	ENSP00000323795.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461842 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727220

African (AFR) AF: 0.00 AC: 0 AN: 33478

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

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112004

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.3
DANN	Benign	0.20
DEOGEN2	Benign	0.024	T;.;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.21	T;T;T;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.032	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.34	N;N;N;.
PhyloP100		0.78
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.50	N;N;N;N
REVEL	Benign	0.024
Sift	Benign	0.26	T;T;T;T
Sift4G	Benign	0.21	T;T;T;T
Polyphen		0.0	B;.;B;B
Vest4		0.10
MutPred		0.25		Gain of disorder (P = 0.036);Gain of disorder (P = 0.036);Gain of disorder (P = 0.036);.;
MVP		0.040
MPC		0.13
ClinPred		0.17	T
GERP RS		-2.7
PromoterAI		0.0012	Neutral
Varity_R		0.080
gMVP		0.028
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs575322146; hg19: chr1-178489993;