NM_001101.5:c.*96delT

Variant names:

• chr7-5527651-CA-C
• rs372205322
• NM_001101.5:c.*96delT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001101.5(ACTB):​c.*96delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 145,404 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000085 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACTB NM_001101.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 0 publications found

Genes affected

ACTB (HGNC:132): (actin beta) This gene encodes one of six different actin proteins. Actins are highly conserved proteins that are involved in cell motility, structure, integrity, and intercellular signaling. The encoded protein is a major constituent of the contractile apparatus and one of the two nonmuscle cytoskeletal actins that are ubiquitously expressed. Mutations in this gene cause Baraitser-Winter syndrome 1, which is characterized by intellectual disability with a distinctive facial appearance in human patients. Numerous pseudogenes of this gene have been identified throughout the human genome. [provided by RefSeq, Aug 2017]

ACTB Gene-Disease associations (from GenCC):

• Baraitser-Winter cerebrofrontofacial syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Baraitser-Winter syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• developmental malformations-deafness-dystonia syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Illumina, Genomics England PanelApp
• ACTB-associated syndromic thrombocytopenia

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101.5. 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
	ACTB	NM_001101.5	MANE Select	c.*96delT		3_prime_UTR	Exon 6 of 6	NP_001092.1	P60709

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTB	ENST00000646664.1	MANE Select	c.*96delT		3_prime_UTR	Exon 6 of 6	ENSP00000494750.1	P60709
	ACTB	ENST00000425660.5	TSL:1	n.*887delT		non_coding_transcript_exon	Exon 7 of 7	ENSP00000409264.1	G5E9R0
	ACTB	ENST00000425660.5	TSL:1	n.*887delT		3_prime_UTR	Exon 7 of 7	ENSP00000409264.1	G5E9R0

Frequencies

GnomAD3 genomes AF: 0.0000138 AC: 2 AN: 145404 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000137

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000847 AC: 10 AN: 1181178 Hom.: 0 Cov.: 30 AF XY: 0.00000848 AC XY: 5 AN XY: 589740

⚠️ 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: 26166

American (AMR) AF: 0.00 AC: 0 AN: 31916

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21446

East Asian (EAS) AF: 0.00 AC: 0 AN: 35254

South Asian (SAS) AF: 0.00 AC: 0 AN: 68934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3436

European-Non Finnish (NFE) AF: 0.00000999 AC: 9 AN: 901234

Other (OTH) AF: 0.0000201 AC: 1 AN: 49742

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000646673), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000138 AC: 2 AN: 145404 Hom.: 0 Cov.: 31 AF XY: 0.0000283 AC XY: 2 AN XY: 70588

African (AFR) AF: 0.00 AC: 0 AN: 39382

American (AMR) AF: 0.000137 AC: 2 AN: 14634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3392

East Asian (EAS) AF: 0.00 AC: 0 AN: 4944

South Asian (SAS) AF: 0.00 AC: 0 AN: 4604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65948

Other (OTH) AF: 0.00 AC: 0 AN: 2012

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.027

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: rs372205322; hg19: chr7-5567282;