rs369051842

Variant names:

• chr6-10409961-G-A
• rs369051842
• NM_001372066.1:c.426C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001372066.1(TFAP2A):​c.426C>T​(p.Leu142Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000967 in 1,575,718 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (1 hom.)
• Consequence: TFAP2A NM_001372066.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.118
• Publications: 1 publications found

Genes affected

TFAP2A (HGNC:11742): (transcription factor AP-2 alpha) The protein encoded by this gene is a transcription factor that binds the consensus sequence 5'-GCCNNNGGC-3'. The encoded protein functions as either a homodimer or as a heterodimer with similar family members. This protein activates the transcription of some genes while inhibiting the transcription of others. Defects in this gene are a cause of branchiooculofacial syndrome (BOFS). Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Dec 2009]

TFAP2A-AS1 (HGNC:40579): (TFAP2A antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.013).
• BP6: Variant 6-10409961-G-A is Benign according to our data. Variant chr6-10409961-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 774641.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.118 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000631 (96/152060) while in subpopulation NFE AF = 0.00109 (74/68004). AF 95% confidence interval is 0.000889. There are 0 homozygotes in GnomAd4. There are 34 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 96 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372066.1. 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
	TFAP2A	NM_001372066.1	MANE Select	c.426C>T	p.Leu142Leu	synonymous	Exon 2 of 7	NP_001358995.1	A0A6E1XE14
	TFAP2A	NM_001042425.3		c.408C>T	p.Leu136Leu	synonymous	Exon 2 of 7	NP_001035890.1	P05549-6
	TFAP2A	NM_001032280.3		c.402C>T	p.Leu134Leu	synonymous	Exon 2 of 7	NP_001027451.1	P05549-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2A	ENST00000379613.10	TSL:1 MANE Select	c.426C>T	p.Leu142Leu	synonymous	Exon 2 of 7	ENSP00000368933.5	A0A6E1XE14
	TFAP2A	ENST00000379608.9	TSL:1	c.402C>T	p.Leu134Leu	synonymous	Exon 2 of 7	ENSP00000368928.3	P05549-5
	TFAP2A	ENST00000466073.5	TSL:1	c.420C>T	p.Leu140Leu	synonymous	Exon 2 of 6	ENSP00000417495.1	C1K3N0

Frequencies

GnomAD3 genomes AF: 0.000631 AC: 96 AN: 152060 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000518 AC: 98 AN: 189182 AF XY: 0.000589

Gnomad AFR exome AF: 0.000181

Gnomad AMR exome AF: 0.000110

Gnomad ASJ exome AF: 0.000445

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000178

Gnomad NFE exome AF: 0.00105

Gnomad OTH exome AF: 0.000400

GnomAD4 exome AF: 0.00100 AC: 1428 AN: 1423658 Hom.: 1 Cov.: 32 AF XY: 0.000951 AC XY: 670 AN XY: 704858

African (AFR) AF: 0.0000922 AC: 3 AN: 32542

American (AMR) AF: 0.000132 AC: 5 AN: 38004

Ashkenazi Jewish (ASJ) AF: 0.000393 AC: 10 AN: 25446

East Asian (EAS) AF: 0.00 AC: 0 AN: 37176

South Asian (SAS) AF: 0.00 AC: 0 AN: 82318

European-Finnish (FIN) AF: 0.000375 AC: 19 AN: 50732

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00124 AC: 1353 AN: 1092718

Other (OTH) AF: 0.000644 AC: 38 AN: 58988

GnomAD4 genome AF: 0.000631 AC: 96 AN: 152060 Hom.: 0 Cov.: 32 AF XY: 0.000458 AC XY: 34 AN XY: 74246

African (AFR) AF: 0.000290 AC: 12 AN: 41402

American (AMR) AF: 0.000327 AC: 5 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00109 AC: 74 AN: 68004

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.000627

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Branchiooculofacial syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.4
DANN	Uncertain	0.98
PhyloP100		0.12
PromoterAI		-0.045	Neutral
Mutation Taster		=100/0	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: rs369051842; hg19: chr6-10410194;