2-27665145-C-G

Variant summary

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

The NM_018158.3(SLC4A1AP):c.709C>G(p.Gln237Glu) 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. 14/21 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: SLC4A1AP NM_018158.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.18

Genes affected

SLC4A1AP (HGNC:13813): (solute carrier family 4 member 1 adaptor protein) Predicted to enable mRNA binding activity. Located in nucleoplasm and plasma membrane. [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=0.071965724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A1AP	NM_018158.3	c.709C>G	p.Gln237Glu	missense_variant	2/14	ENST00000326019.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A1AP	ENST00000326019.11	c.709C>G	p.Gln237Glu	missense_variant	2/14	1	NM_018158.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Mar 31, 2023

The c.871C>G (p.Q291E) alteration is located in exon 2 (coding exon 2) of the SLC4A1AP gene. This alteration results from a C to G substitution at nucleotide position 871, causing the glutamine (Q) at amino acid position 291 to be replaced by a glutamic acid (E). 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	0.081
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	17
Dann	Benign	0.73
DEOGEN2	Benign	0.014	T;T;.;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.75	D
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.072	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.040	N;N;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.82	N;.;.;.
REVEL	Benign	0.070
Sift	Benign	1.0	T;.;.;.
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.014	B;B;.;.
Vest4		0.15
MutPred		0.31		Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);.;.;
MVP		0.24
MPC		0.29
ClinPred		0.24	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.28

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: chr2-27888012;