1-46673061-G-C

Variant names:

• chr1-46673061-G-C
• rs796522685
• NM_001145474.4:c.226G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001145474.4(TEX38):​c.226G>C​(p.Gly76Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,399,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G76S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TEX38 NM_001145474.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.22
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX38	NM_001145474.4	c.226G>C	p.Gly76Arg	missense_variant	Exon 2 of 2	ENST00000334122.5	NP_001138946.1
TEX38	NM_001300863.2	c.64G>C	p.Gly22Arg	missense_variant	Exon 2 of 2		NP_001287792.1
TEX38	XM_011541421.4	c.229G>C	p.Gly77Arg	missense_variant	Exon 2 of 2		XP_011539723.1
TEX38	NM_001300864.2	c.-3G>C		5_prime_UTR_variant	Exon 2 of 2		NP_001287793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX38	ENST00000334122.5	c.226G>C	p.Gly76Arg	missense_variant	Exon 2 of 2	1	NM_001145474.4	ENSP00000455854.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399418 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690210

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078978

Other (OTH) AF: 0.00 AC: 0 AN: 58004

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.099	T;T;T
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Pathogenic	0.45	D
MetaRNN	Pathogenic	0.82	D;D;D
MutationAssessor	Benign	1.7	.;L;.
PhyloP100		5.2
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-6.6	D;D;D
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.62, 0.65
MVP		0.83
GERP RS		5.5
Varity_R		0.71
gMVP		0.47
Mutation Taster		=73/27	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: rs796522685; hg19: chr1-47138733;