NM_016176.6:c.1043C>T

Variant names:

• chr1-1217537-G-A
• rs113021852
• NM_016176.6:c.1043C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_016176.6(SDF4):​c.1043C>T​(p.Ala348Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00045 in 1,611,946 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (0 hom.)
• Consequence: SDF4 NM_016176.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.57
• Publications: 3 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDF4	NM_016176.6	c.1043C>T	p.Ala348Val	missense_variant	Exon 7 of 7	ENST00000360001.12	NP_057260.3
SDF4	XM_047422111.1	c.1064C>T	p.Ala355Val	missense_variant	Exon 7 of 7		XP_047278067.1
SDF4	NM_016547.3	c.*133C>T		3_prime_UTR_variant	Exon 7 of 7		NP_057631.2
SDF4	XM_047422112.1	c.*133C>T		3_prime_UTR_variant	Exon 7 of 7		XP_047278068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDF4	ENST00000360001.12	c.1043C>T	p.Ala348Val	missense_variant	Exon 7 of 7	1	NM_016176.6	ENSP00000353094.7

Frequencies

GnomAD3 genomes AF: 0.000302 AC: 46 AN: 152114 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000420 AC: 104 AN: 247782 AF XY: 0.000386

Gnomad AFR exome AF: 0.0000625

Gnomad AMR exome AF: 0.000407

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000756

Gnomad OTH exome AF: 0.000827

GnomAD4 exome AF: 0.000466 AC: 680 AN: 1459832 Hom.: 0 Cov.: 31 AF XY: 0.000453 AC XY: 329 AN XY: 726118

African (AFR) AF: 0.0000897 AC: 3 AN: 33460

American (AMR) AF: 0.000358 AC: 16 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.000576 AC: 640 AN: 1111284

Other (OTH) AF: 0.000315 AC: 19 AN: 60326

GnomAD4 genome AF: 0.000302 AC: 46 AN: 152114 Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15 AN XY: 74312

African (AFR) AF: 0.000169 AC: 7 AN: 41436

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000674 Hom.: 0

Bravo AF: 0.000404

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00140 AC: 12

ExAC AF: 0.000338 AC: 41

EpiCase AF: 0.000545

EpiControl AF: 0.000831

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1064C>T (p.A355V) alteration is located in exon 7 (coding exon 6) of the SDF4 gene. This alteration results from a C to T substitution at nucleotide position 1064, causing the alanine (A) at amino acid position 355 to be replaced by a valine (V). 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	0.73
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.8	L
PhyloP100		9.6
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.019	D
Polyphen		0.92	P
Vest4		0.76
MVP		0.43
MPC		1.1
ClinPred		0.12	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.76
Mutation Taster		=41/59	disease causing

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

Other links and lift over

dbSNP: rs113021852; hg19: chr1-1152917; COSMIC: COSV108745378; COSMIC: COSV108745378;