chr1-46673445-T-A

Position:

• chr1-46673445-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001145474.4(TEX38):​c.610T>A​(p.Ser204Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 1,549,322 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0060 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (118 hom.)
• Consequence: TEX38 NM_001145474.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.579

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034383535).
• BP6: Variant 1-46673445-T-A is Benign according to our data. Variant chr1-46673445-T-A is described in ClinVar as [Benign]. Clinvar id is 769513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00604 (920/152300) while in subpopulation EAS AF= 0.0335 (174/5190). AF 95% confidence interval is 0.0302. There are 10 homozygotes in gnomad4. There are 497 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX38	NM_001145474.4	c.610T>A	p.Ser204Thr	missense_variant	2/2	ENST00000334122.5	NP_001138946.1
TEX38	NM_001300863.2	c.448T>A	p.Ser150Thr	missense_variant	2/2		NP_001287792.1
TEX38	NM_001300864.2	c.382T>A	p.Ser128Thr	missense_variant	2/2		NP_001287793.1
TEX38	XM_011541421.4	c.613T>A	p.Ser205Thr	missense_variant	2/2		XP_011539723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX38	ENST00000334122.5	c.610T>A	p.Ser204Thr	missense_variant	2/2	1	NM_001145474.4	ENSP00000455854	P1
TEX38	ENST00000564373.1	c.448T>A	p.Ser150Thr	missense_variant	2/2	1		ENSP00000456524
TEX38	ENST00000415500.1	c.382T>A	p.Ser128Thr	missense_variant	2/2	1		ENSP00000456892
ATPAF1	ENST00000525633.1	n.314+109A>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00602 AC: 916 AN: 152182 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0321

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.0338

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.00861

GnomAD3 exomes AF: 0.0136 AC: 2129 AN: 156080 Hom.: 56 AF XY: 0.0125 AC XY: 1027 AN XY: 82408

Gnomad AFR exome AF: 0.000736

Gnomad AMR exome AF: 0.0483

Gnomad ASJ exome AF: 0.00275

Gnomad EAS exome AF: 0.0360

Gnomad SAS exome AF: 0.0184

Gnomad FIN exome AF: 0.000365

Gnomad NFE exome AF: 0.000824

Gnomad OTH exome AF: 0.0110

GnomAD4 exome AF: 0.00414 AC: 5777 AN: 1397022 Hom.: 118 Cov.: 32 AF XY: 0.00440 AC XY: 3028 AN XY: 688782

Gnomad4 AFR exome AF: 0.000729

Gnomad4 AMR exome AF: 0.0475

Gnomad4 ASJ exome AF: 0.00419

Gnomad4 EAS exome AF: 0.0377

Gnomad4 SAS exome AF: 0.0190

Gnomad4 FIN exome AF: 0.000531

Gnomad4 NFE exome AF: 0.000652

Gnomad4 OTH exome AF: 0.00650

GnomAD4 genome AF: 0.00604 AC: 920 AN: 152300 Hom.: 10 Cov.: 32 AF XY: 0.00667 AC XY: 497 AN XY: 74472

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.0326

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.0335

Gnomad4 SAS AF: 0.0255

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.000559

Gnomad4 OTH AF: 0.00852

Alfa AF: 0.00263 Hom.: 8

Bravo AF: 0.00850

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00126 AC: 4

ExAC AF: 0.00633 AC: 164

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	12
DANN	Benign	0.60
DEOGEN2	Benign	0.011	T;T;T
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.39	T;T;T
MetaRNN	Benign	0.0034	T;T;T
MutationAssessor	Uncertain	2.1	M;.;.
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.7	N;N;N
Sift	Benign	0.26	T;T;T
Sift4G	Benign	0.47	T;T;T
Polyphen		0.56	P;.;.
Vest4		0.10
GERP RS		3.9
Varity_R		0.10
gMVP		0.21

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: rs77202675; hg19: chr1-47139117; COSMIC: COSV61906068; COSMIC: COSV61906068;