chr1-38991483-A-T

Position:

• chr1-38991483-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000432648.8(AKIRIN1):​c.103A>T​(p.Thr35Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000156 in 1,283,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: AKIRIN1 ENST00000432648.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83

Genes affected

AKIRIN1 (HGNC:25744): (akirin 1) Predicted to enable transcription coregulator activity. Predicted to be involved in several processes, including myoblast migration involved in skeletal muscle regeneration; negative regulation of satellite cell differentiation; and positive regulation of lamellipodium assembly. Located in nuclear membrane and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07178798).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKIRIN1	NM_024595.3	c.103A>T	p.Thr35Ser	missense_variant	1/5	ENST00000432648.8	NP_078871.1
AKIRIN1	NM_001136275.2	c.103A>T	p.Thr35Ser	missense_variant	1/4		NP_001129747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKIRIN1	ENST00000432648.8	c.103A>T	p.Thr35Ser	missense_variant	1/5	1	NM_024595.3	ENSP00000392678.3
AKIRIN1	ENST00000446189.6	c.103A>T	p.Thr35Ser	missense_variant	1/4	2		ENSP00000389866.2
AKIRIN1	ENST00000372984.8	c.103A>T	p.Thr35Ser	missense_variant	1/4	2		ENSP00000362075.4
AKIRIN1	ENST00000531822.1	c.-15A>T		upstream_gene_variant		5		ENSP00000436372.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000156 AC: 2 AN: 1283318 Hom.: 0 Cov.: 36 AF XY: 0.00000317 AC XY: 2 AN XY: 629994

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: 9.70e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

The c.103A>T (p.T35S) alteration is located in exon 1 (coding exon 1) of the AKIRIN1 gene. This alteration results from a A to T substitution at nucleotide position 103, causing the threonine (T) at amino acid position 35 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.89
DEOGEN2	Benign	0.059	T;.;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.60	T;T;T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.072	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.010	N;N;.
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.14	N;N;N
REVEL	Benign	0.066
Sift	Benign	0.94	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0020	B;.;B
Vest4		0.10
MutPred		0.21		Loss of glycosylation at T35 (P = 0.0744);Loss of glycosylation at T35 (P = 0.0744);Loss of glycosylation at T35 (P = 0.0744);
MVP		0.093
MPC		0.30
ClinPred		0.48	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.052
gMVP		0.27

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-39457155;