2-232457029-G-C

Variant names:

• chr2-232457029-G-C
• NM_001631.5:c.431G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001631.5(ALPI):​c.431G>C​(p.Arg144Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R144H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ALPI NM_001631.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.69

Genes affected

ALPI (HGNC:437): (alkaline phosphatase, intestinal) There are at least four distinct but related alkaline phosphatases: intestinal, placental, placental-like, and liver/bone/kidney (tissue non-specific). The intestinal alkaline phosphatase gene encodes a digestive brush-border enzyme. This enzyme is a component of the gut mucosal defense system and is thought to function in the detoxification of lipopolysaccharide, and in the prevention of bacterial translocation in the gut. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28191683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALPI	NM_001631.5	c.431G>C	p.Arg144Pro	missense_variant	Exon 4 of 11	ENST00000295463.4	NP_001622.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALPI	ENST00000295463.4	c.431G>C	p.Arg144Pro	missense_variant	Exon 4 of 11	1	NM_001631.5	ENSP00000295463.3
ALPI	ENST00000457560.1	n.*360G>C		non_coding_transcript_exon_variant	Exon 3 of 10	5		ENSP00000413068.1
ALPI	ENST00000457560.1	n.*360G>C		3_prime_UTR_variant	Exon 3 of 10	5		ENSP00000413068.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461248 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726930

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	0.0070
DANN	Benign	0.67
DEOGEN2	Uncertain	0.69	D
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.076	T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.28	T
MetaSVM	Uncertain	0.081	D
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.19	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.37
Sift	Benign	0.28	T
Sift4G	Benign	0.31	T
Polyphen		0.86	P
Vest4		0.17
MutPred		0.43		Loss of MoRF binding (P = 0.0065);
MVP		0.51
MPC		0.30
ClinPred		0.84	D
GERP RS		-11
Varity_R		0.24
gMVP		0.83

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: chr2-233321739;