NM_005681.4:c.970_972delGAA

Variant names:

• chr1-222563285-GTTC-G
• rs759862116
• NM_005681.4:c.970_972delGAA

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PM4_Supporting BS2

The NM_005681.4(TAF1A):​c.970_972delGAA​(p.Glu324del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000243 in 1,612,076 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00026 (0 hom.)
• Consequence: TAF1A NM_005681.4 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.82
• Publications: 0 publications found

Genes affected

TAF1A (HGNC:11532): (TATA-box binding protein associated factor, RNA polymerase I subunit A) This gene encodes a subunit of the RNA polymerase I complex, Selectivity Factor I (SLI). The encoded protein is a TATA box-binding protein-associated factor that plays a role in the assembly of the RNA polymerase I preinitiation complex. Alternate splicing results in multiple transcript variants encoding multiple isoforms.[provided by RefSeq, Jan 2011]

TAF1A Gene-Disease associations (from GenCC):

• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_005681.4. Strenght limited to Supporting due to length of the change: 1aa.
• BS2: High AC in GnomAd4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005681.4. 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
	TAF1A	NM_005681.4	MANE Select	c.970_972delGAA	p.Glu324del	conservative_inframe_deletion	Exon 9 of 11	NP_005672.1	Q15573-1
	TAF1A	NM_001201536.1		c.970_972delGAA	p.Glu324del	conservative_inframe_deletion	Exon 9 of 12	NP_001188465.1	A8K4K5
	TAF1A	NM_139352.2		c.628_630delGAA	p.Glu210del	conservative_inframe_deletion	Exon 8 of 11	NP_647603.1	Q15573-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1A	ENST00000352967.9	TSL:1 MANE Select	c.970_972delGAA	p.Glu324del	conservative_inframe_deletion	Exon 9 of 11	ENSP00000327072.6	Q15573-1
	TAF1A	ENST00000972077.1		c.1105_1107delGAA	p.Glu369del	conservative_inframe_deletion	Exon 10 of 12	ENSP00000642136.1
	TAF1A	ENST00000350027.8	TSL:2	c.970_972delGAA	p.Glu324del	conservative_inframe_deletion	Exon 9 of 12	ENSP00000339976.4	Q15573-1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152080 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

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: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000602 AC: 15 AN: 249056 AF XY: 0.0000519

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000548

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000262 AC: 383 AN: 1459996 Hom.: 0 AF XY: 0.000251 AC XY: 182 AN XY: 726340

African (AFR) AF: 0.0000300 AC: 1 AN: 33370

American (AMR) AF: 0.00 AC: 0 AN: 44170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39564

South Asian (SAS) AF: 0.00 AC: 0 AN: 85992

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.000337 AC: 374 AN: 1111378

Other (OTH) AF: 0.000116 AC: 7 AN: 60308

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152080 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74298

African (AFR) AF: 0.0000483 AC: 2 AN: 41416

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.0000529

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.22		Position offset: 11

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

Other links and lift over

dbSNP: rs759862116; hg19: chr1-222736627;