NM_000583.4:c.1307C>G

Variant names:

• chr4-71752606-G-C
• NM_000583.4:c.1307C>G

Variant summary

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

The NM_000583.4(GC):​c.1307C>G​(p.Thr436Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GC NM_000583.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.459

Genes affected

GC (HGNC:4187): (GC vitamin D binding protein) The protein encoded by this gene belongs to the albumin gene family. It is a multifunctional protein found in plasma, ascitic fluid, cerebrospinal fluid and on the surface of many cell types. It binds to vitamin D and its plasma metabolites and transports them to target tissues. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GC	NM_000583.4	c.1307C>G	p.Thr436Arg	missense_variant	Exon 11 of 13	ENST00000273951.13	NP_000574.2
GC	NM_001204307.1	c.1364C>G	p.Thr455Arg	missense_variant	Exon 12 of 14		NP_001191236.1
GC	NM_001204306.1	c.1307C>G	p.Thr436Arg	missense_variant	Exon 12 of 14		NP_001191235.1
GC	XM_006714177.3	c.1262+1805C>G		intron_variant	Intron 10 of 11		XP_006714240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GC	ENST00000273951.13	c.1307C>G	p.Thr436Arg	missense_variant	Exon 11 of 13	1	NM_000583.4	ENSP00000273951.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461126 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 726928

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: 0.00000180

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	0.074
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.11
DANN	Benign	0.89
DEOGEN2	Benign	0.018	.;.;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.42	T;T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.99	N;N;N
REVEL	Benign	0.041
Sift	Benign	0.19	T;T;T
Sift4G	Benign	0.41	T;T;T
Polyphen		0.90	.;.;P
Vest4		0.26
MutPred		0.45		Gain of methylation at T436 (P = 0.02);.;Gain of methylation at T436 (P = 0.02);
MVP		0.14
MPC		0.17
ClinPred		0.34	T
GERP RS		-2.7
Varity_R		0.15
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.23		Position offset: 44

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: chr4-72618323;