NM_016176.6:c.419G>C

Variant names:

• chr1-1223855-C-G
• NM_016176.6:c.419G>C

Variant summary

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

The NM_016176.6(SDF4):​c.419G>C​(p.Arg140Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,790 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R140C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SDF4 NM_016176.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95

Genes affected

SDF4 (HGNC:24188): (stromal cell derived factor 4) This gene encodes a stromal cell derived factor that is a member of the CREC protein family. The encoded protein contains six EF-hand motifs and calcium-binding motifs. This protein localizes to the Golgi lumen and may be involved in regulating calcium dependent cellular activities. [provided by RefSeq, Sep 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
SDF4	NM_016176.6	c.419G>C	p.Arg140Pro	missense_variant	Exon 3 of 7	ENST00000360001.12	NP_057260.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDF4	ENST00000360001.12	c.419G>C	p.Arg140Pro	missense_variant	Exon 3 of 7	1	NM_016176.6	ENSP00000353094.7
SDF4	ENST00000263741.12	c.419G>C	p.Arg140Pro	missense_variant	Exon 3 of 7	1		ENSP00000263741.8
SDF4	ENST00000403997.2	c.242G>C	p.Arg81Pro	missense_variant	Exon 2 of 5	3		ENSP00000384207.2
SDF4	ENST00000465727.5	n.440G>C		non_coding_transcript_exon_variant	Exon 3 of 7	2		ENSP00000435962.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451790 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 722562

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	16
DANN	Benign	0.89
DEOGEN2	Uncertain	0.52	D;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.73
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.085	D
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Uncertain	0.43
Sift	Benign	0.38	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.0020	B;B
Vest4		0.83
MutPred		0.42		Gain of glycosylation at T144 (P = 0.0388);Gain of glycosylation at T144 (P = 0.0388);
MVP		0.77
MPC		0.55
ClinPred		0.15	T
GERP RS		-1.1
Varity_R		0.47
gMVP		0.73

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: chr1-1159235;