chr1-119798580-T-C

Position:

• chr1-119798580-T-C

Variant summary

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

The NM_032044.4(REG4):​c.326A>G​(p.Asp109Gly) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: REG4 NM_032044.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71

Genes affected

REG4 (HGNC:22977): (regenerating family member 4) Enables heparin binding activity and mannan binding activity. Predicted to act upstream of or within response to bacterium. Located in cytoplasm. [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, 0.752

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REG4	NM_032044.4	c.326A>G	p.Asp109Gly	missense_variant	5/6	ENST00000256585.10	NP_114433.1
REG4	NM_001159352.2	c.326A>G	p.Asp109Gly	missense_variant	6/7		NP_001152824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REG4	ENST00000256585.10	c.326A>G	p.Asp109Gly	missense_variant	5/6	1	NM_032044.4	ENSP00000256585.5
REG4	ENST00000354219.5	c.326A>G	p.Asp109Gly	missense_variant	6/7	1		ENSP00000346158.1
REG4	ENST00000530654.1	c.303+1145A>G		intron_variant		5		ENSP00000437135.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

May 29, 2024

The c.326A>G (p.D109G) alteration is located in exon 6 (coding exon 4) of the REG4 gene. This alteration results from a A to G substitution at nucleotide position 326, causing the aspartic acid (D) at amino acid position 109 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	Pathogenic	0.70
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.57	.;T
M_CAP	Benign	0.0078	T
MetaRNN	Pathogenic	0.75	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.2	M;M
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-5.3	D;D
REVEL	Benign	0.19
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.055	T;T
Polyphen		0.037	B;B
Vest4		0.62
MutPred		0.75		Gain of MoRF binding (P = 0.0727);Gain of MoRF binding (P = 0.0727);
MVP		0.30
MPC		0.36
ClinPred		0.94	D
GERP RS		3.9
Varity_R		0.32
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: chr1-120341203;