chrX-103330974-G-C

Position:

• chrX-103330974-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001348258.2(TCEAL7):​c.-91-3G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.62 (16585 hom., 19699 hem., cov: 22)
  • Exomes 𝑓: 0.51 (396 hom. 421 hem.)
  • Failed GnomAD Quality Control
• Consequence: TCEAL7 NM_001348258.2 splice_region, intron
• Scores: Splicing: ADA: 0.00004452
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363

Genes affected

TCEAL7 (HGNC:28336): (transcription elongation factor A like 7) Predicted to enable WW domain binding activity. Involved in negative regulation of NF-kappaB transcription factor activity and negative regulation of transcription, DNA-templated. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCEAL7	NM_152278.5	c.-94G>C		5_prime_UTR_variant	2/3	ENST00000332431.5	NP_689491.1
TCEAL7	NM_001348258.2	c.-91-3G>C		splice_region_variant, intron_variant			NP_001335187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCEAL7	ENST00000332431.5	c.-94G>C		5_prime_UTR_variant	2/3	1	NM_152278.5	ENSP00000329794.4
TCEAL7	ENST00000372666.1	c.-91-3G>C		splice_region_variant, intron_variant		2		ENSP00000361751.1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 68240 AN: 109842 Hom.: 16581 Cov.: 22 AF XY: 0.611 AC XY: 19639 AN XY: 32126

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.611

GnomAD4 exome AF: 0.505 AC: 1810 AN: 3582 Hom.: 396 Cov.: 0 AF XY: 0.508 AC XY: 421 AN XY: 828

Gnomad4 AFR exome AF: 0.922

Gnomad4 AMR exome AF: 0.595

Gnomad4 ASJ exome AF: 0.652

Gnomad4 EAS exome AF: 0.541

Gnomad4 SAS exome AF: 0.782

Gnomad4 FIN exome AF: 0.446

Gnomad4 NFE exome AF: 0.469

Gnomad4 OTH exome AF: 0.494

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.621 AC: 68297 AN: 109894 Hom.: 16585 Cov.: 22 AF XY: 0.612 AC XY: 19699 AN XY: 32188

Gnomad4 AFR AF: 0.899

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.742

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.611

Alfa AF: 0.557 Hom.: 4269

Bravo AF: 0.647

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000045
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1045761; hg19: chrX-102585902; COSMIC: COSV60125190;