chr1-46672945-A-G

Variant names:

• chr1-46672945-A-G
• rs1336616105
• NM_001145474.4:c.110A>G

Variant summary

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

The NM_001145474.4(TEX38):​c.110A>G​(p.His37Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,150 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: TEX38 NM_001145474.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.87

Genes affected

TEX38 (HGNC:29589): (testis expressed 38) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ATPAF1 (HGNC:18803): (ATP synthase mitochondrial F1 complex assembly factor 1) This gene encodes an assembly factor for the F(1) component of the mitochondrial ATP synthase. This protein binds specifically to the F1 beta subunit and is thought to prevent this subunit from forming nonproductive homooligomers during enzyme assembly. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Aug 2011]

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 rank	MANE	Protein	UniProt
TEX38	NM_001145474.4	c.110A>G	p.His37Arg	missense_variant	Exon 2 of 2	ENST00000334122.5	NP_001138946.1
TEX38	XM_011541421.4	c.113A>G	p.His38Arg	missense_variant	Exon 2 of 2		XP_011539723.1
TEX38	NM_001300863.2	c.-46-7A>G		splice_region_variant, intron_variant	Intron 1 of 1		NP_001287792.1
TEX38	NM_001300864.2	c.-40-79A>G		intron_variant	Intron 1 of 1		NP_001287793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX38	ENST00000334122.5	c.110A>G	p.His37Arg	missense_variant	Exon 2 of 2	1	NM_001145474.4	ENSP00000455854.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152150 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: 0.00

Gnomad OTH AF: 0.000479

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152150 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74330

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000479

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.110A>G (p.H37R) alteration is located in exon 2 (coding exon 2) of the TEX38 gene. This alteration results from a A to G substitution at nucleotide position 110, causing the histidine (H) at amino acid position 37 to be replaced by an arginine (R). 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	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.076	T;T
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.65	T;T
M_CAP	Uncertain	0.29	D
MetaRNN	Uncertain	0.62	D;D
MutationAssessor	Benign	1.7	.;L
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-5.5	D;D
Sift	Uncertain	0.016	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	.;D
Vest4		0.62
MVP		0.77
GERP RS		4.2
Varity_R		0.41
gMVP		0.61

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

LitVar

Other links and lift over

dbSNP: rs1336616105; hg19: chr1-47138617;