9-108936322-C-T

Variant names:

• chr9-108936322-C-T
• rs1050266328
• NM_017832.4:c.146C>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_017832.4(ABITRAM):​c.146C>T​(p.Thr49Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ABITRAM NM_017832.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57

Genes affected

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABITRAM	NM_017832.4	c.146C>T	p.Thr49Ile	missense_variant	Exon 3 of 6	ENST00000322940.11	NP_060302.1
ABITRAM	NM_001410990.1	c.146C>T	p.Thr49Ile	missense_variant	Exon 3 of 4		NP_001397919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABITRAM	ENST00000322940.11	c.146C>T	p.Thr49Ile	missense_variant	Exon 3 of 6	1	NM_017832.4	ENSP00000363753.3
ABITRAM	ENST00000445175.1	c.41C>T	p.Thr14Ile	missense_variant	Exon 2 of 5	3		ENSP00000398018.1
ABITRAM	ENST00000374624.7	c.146C>T	p.Thr49Ile	missense_variant	Exon 3 of 4	3		ENSP00000363754.3
ABITRAM	ENST00000466200.1	n.*247C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 250930 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135644

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461104 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726854

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;T;T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.80	D;D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Pathogenic	2.9	M;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.031	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.97
MutPred		0.52		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);.;
MVP		0.75
MPC		0.62
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.56
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1050266328; hg19: chr9-111698602;