rs1414123470

Variant names:

• chr1-178520822-A-C
• rs1414123470
• NM_032126.5:c.491A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-178520822-A-C
• chr1-178520822-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032126.5(TEX35):​c.491A>C​(p.Gln164Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. Q164R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TEX35 NM_032126.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.469
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09655097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX35	NM_032126.5	c.491A>C	p.Gln164Pro	missense_variant	Exon 7 of 9	ENST00000319416.7	NP_115502.2
TEX35	NM_001170722.2	c.515A>C	p.Gln172Pro	missense_variant	Exon 7 of 9		NP_001164193.1
TEX35	NM_001170723.2	c.491A>C	p.Gln164Pro	missense_variant	Exon 7 of 9		NP_001164194.1
TEX35	NM_001170724.2	c.491A>C	p.Gln164Pro	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.491A>C	p.Gln164Pro	missense_variant	Exon 7 of 9	1	NM_032126.5	ENSP00000323795.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 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: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

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	0.093
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.50
DEOGEN2	Benign	0.020	T;.;.;.
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.41	T;T;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.097	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L;L;.
PhyloP100		0.47
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.1	D;D;D;D
REVEL	Benign	0.016
Sift	Benign	0.18	T;T;T;T
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		0.0090	B;.;B;B
Vest4		0.24
MutPred		0.15		Gain of glycosylation at Q164 (P = 0.0033);Gain of glycosylation at Q164 (P = 0.0033);Gain of glycosylation at Q164 (P = 0.0033);.;
MVP		0.061
MPC		0.17
ClinPred		0.091	T
GERP RS		0.10
PromoterAI		0.030	Neutral
Varity_R		0.46
gMVP		0.031
Mutation Taster		=92/8	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: rs1414123470; hg19: chr1-178489957;