NM_001297563.2:c.-149G>A

Variant names:

• chrX-13659720-G-A
• rs748473667
• NM_001297563.2:c.-149G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001297563.2(TCEANC):​c.-149G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., 8 hem., cov: 20)
  • Exomes 𝑓: 0.00050 (0 hom. 1 hem.)
• Consequence: TCEANC NM_001297563.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.230
• Publications: 0 publications found

Genes affected

TCEANC (HGNC:28277): (transcription elongation factor A N-terminal and central domain containing) Predicted to be involved in transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TCEANC Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: XL Classification: LIMITED Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19279006).
• BP6: Variant X-13659720-G-A is Benign according to our data. Variant chrX-13659720-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3771297.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 8 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297563.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEANC	NM_001297563.2	MANE Select	c.-149G>A		5_prime_UTR	Exon 3 of 5	NP_001284492.1	Q8N8B7-1
	TCEANC	NM_152634.4		c.34G>A	p.Gly12Ser	missense	Exon 3 of 4	NP_689847.2
	TCEANC	NM_001297564.2		c.-8-2781G>A		intron	N/A	NP_001284493.1	Q8N8B7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEANC	ENST00000696128.1	MANE Select	c.-149G>A		5_prime_UTR	Exon 3 of 5	ENSP00000512421.1	Q8N8B7-1
	TCEANC	ENST00000544987.3	TSL:5	c.34G>A	p.Gly12Ser	missense	Exon 3 of 4	ENSP00000440038.2	Q8N8B7-2
	TCEANC	ENST00000696126.2		c.-314G>A		5_prime_UTR	Exon 3 of 5	ENSP00000512419.2	Q8N8B7-1

Frequencies

GnomAD3 genomes AF: 0.000353 AC: 38 AN: 107505 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.0000684

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: 0.000672

Gnomad OTH AF: 0.000703

GnomAD2 exomes AF: 0.00 AC: 0 AN: 800 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000497 AC: 2 AN: 4021 Hom.: 0 Cov.: 0 AF XY: 0.000803 AC XY: 1 AN XY: 1245

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 45

American (AMR) AF: 0.00 AC: 0 AN: 94

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 196

East Asian (EAS) AF: 0.00 AC: 0 AN: 31

South Asian (SAS) AF: 0.00 AC: 0 AN: 950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 9

European-Non Finnish (NFE) AF: 0.000951 AC: 2 AN: 2102

Other (OTH) AF: 0.00 AC: 0 AN: 178

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000353 AC: 38 AN: 107541 Hom.: 0 Cov.: 20 AF XY: 0.000265 AC XY: 8 AN XY: 30183

African (AFR) AF: 0.0000682 AC: 2 AN: 29319

American (AMR) AF: 0.00 AC: 0 AN: 10074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2613

East Asian (EAS) AF: 0.00 AC: 0 AN: 3445

South Asian (SAS) AF: 0.00 AC: 0 AN: 2376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5325

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 209

European-Non Finnish (NFE) AF: 0.000672 AC: 35 AN: 52072

Other (OTH) AF: 0.000695 AC: 1 AN: 1438

Alfa AF: 0.000378 Hom.: 3

Bravo AF: 0.000355

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00173 AC: 5

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.81
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.23
PrimateAI	Benign	0.41	T
Polyphen		0.99	D
Vest4		0.090
MutPred		0.33		Gain of glycosylation at G12 (P = 0.0239)
MVP		0.63
ClinPred		0.11	T
GERP RS		-0.88
PromoterAI		0.017	Neutral
gMVP		0.099
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs748473667; hg19: chrX-13677839;