6-131145372-T-G

Variant summary

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

The NM_016377.4(AKAP7):c.107T>G(p.Val36Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AKAP7 NM_016377.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.352

Genes affected

AKAP7 (HGNC:377): (A-kinase anchoring protein 7) This gene encodes a member of the A-kinase anchoring protein (AKAP) family, a group of functionally related proteins that bind to a regulatory subunit (RII) of cAMP-dependent protein kinase A (PKA) and target the enzyme to specific subcellular compartments. AKAPs have a common RII-binding domain, but contain different targeting motifs responsible for directing PKA to distinct intracellular locations. Three alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Apr 2011]

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=0.07578841).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AKAP7	NM_016377.4	c.107T>G	p.Val36Gly	missense_variant	2/8	ENST00000431975.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AKAP7	ENST00000431975.7	c.107T>G	p.Val36Gly	missense_variant	2/8	2	NM_016377.4	P1
AKAP7	ENST00000683794.1	c.107T>G	p.Val36Gly	missense_variant	2/8
AKAP7	ENST00000541650.5	c.104T>G	p.Val35Gly	missense_variant	2/8	5
AKAP7	ENST00000366358.2	n.462T>G		non_coding_transcript_exon_variant	2/5	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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

Jan 02, 2024

The c.107T>G (p.V36G) alteration is located in exon 2 (coding exon 2) of the AKAP7 gene. This alteration results from a T to G substitution at nucleotide position 107, causing the valine (V) at amino acid position 36 to be replaced by a glycine (G). 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	0.088
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	6.8
Dann	Benign	0.97
DEOGEN2	Benign	0.015	T;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.076	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.13	N;N
REVEL	Benign	0.047
Sift	Uncertain	0.027	D;D
Sift4G	Benign	0.37	T;T
Polyphen		0.16	B;.
Vest4		0.17
MutPred		0.26		Loss of stability (P = 0.0085);.;
MVP		0.44
MPC		0.035
ClinPred		0.12	T
GERP RS		0.12
Varity_R		0.064
gMVP		0.19

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: chr6-131466512;