NM_003798.4:c.1925A>G

Variant names:

• chr9-108943978-T-C
• rs1564117888
• NM_003798.4:c.1925A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003798.4(CTNNAL1):​c.1925A>G​(p.Gln642Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CTNNAL1 NM_003798.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.32
• Publications: 0 publications found

Genes affected

CTNNAL1 (HGNC:2512): (catenin alpha like 1) Predicted to enable actin filament binding activity and cadherin binding activity. Acts upstream of or within Rho protein signal transduction. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ABITRAM (HGNC:1364): (actin binding transcription modulator) Predicted to enable actin filament binding activity and actin monomer binding activity. Predicted to be involved in dendrite morphogenesis; regulation of actin filament polymerization; and regulation of filopodium assembly. Predicted to be located in growth cone. Predicted to be active in several cellular components, including dendrite; filopodium tip; and lamellipodium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16434523).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003798.4. 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
	CTNNAL1	NM_003798.4	MANE Select	c.1925A>G	p.Gln642Arg	missense	Exon 16 of 19	NP_003789.1	Q9UBT7-1
	CTNNAL1	NM_001286974.2		c.1925A>G	p.Gln642Arg	missense	Exon 16 of 19	NP_001273903.1	Q9UBT7-2
	ABITRAM	NM_001410990.1		c.262-6529T>C		intron	N/A	NP_001397919.1	X6R8U7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNAL1	ENST00000325551.9	TSL:1 MANE Select	c.1925A>G	p.Gln642Arg	missense	Exon 16 of 19	ENSP00000320434.4	Q9UBT7-1
	CTNNAL1	ENST00000374595.8	TSL:1	c.1925A>G	p.Gln642Arg	missense	Exon 16 of 19	ENSP00000363723.4	Q9UBT7-2
	CTNNAL1	ENST00000863428.1		c.1925A>G	p.Gln642Arg	missense	Exon 16 of 19	ENSP00000533487.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251080 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

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: 0.00000137 AC: 2 AN: 1461514 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727020

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.0000448 AC: 2 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111842

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Benign	0.89
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.086
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.40	N
PhyloP100		2.3
PrimateAI	Benign	0.39	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.18
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.31
MutPred		0.51		Loss of ubiquitination at K646 (P = 0.0331)
MVP		0.48
MPC		0.13
ClinPred		0.64	D
GERP RS		5.7
Varity_R		0.082
gMVP		0.11
Mutation Taster		=83/17	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: rs1564117888; hg19: chr9-111706258;