1-1217537-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016176.6(SDF4):​c.1043C>A​(p.Ala348Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,114 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. A348V) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SDF4 NM_016176.6 missense
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016176.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDF4	NM_016176.6	MANE Select	c.1043C>A	p.Ala348Glu	missense	Exon 7 of 7	NP_057260.3
	SDF4	NM_016547.3		c.*133C>A		3_prime_UTR	Exon 7 of 7	NP_057631.2	A0A5F9UJX7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDF4	ENST00000360001.12	TSL:1 MANE Select	c.1043C>A	p.Ala348Glu	missense	Exon 7 of 7	ENSP00000353094.7	A0A5F9UP49
	SDF4	ENST00000263741.12	TSL:1	c.*133C>A		3_prime_UTR	Exon 7 of 7	ENSP00000263741.8	A0A5F9UJX7
	SDF4	ENST00000900950.1		c.1115C>A	p.Ala372Glu	missense	Exon 7 of 7	ENSP00000571009.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152114 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152114 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74312

African (AFR) AF: 0.0000241 AC: 1 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 68016

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

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.2	L
PhyloP100		9.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.43
Sift	Benign	0.22	T
Sift4G	Uncertain	0.0050	D
Polyphen		0.68	P
Vest4		0.79
MutPred		0.62		Gain of disorder (P = 0.0126)
MVP		0.53
MPC		1.2
ClinPred		0.85	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.88
Mutation Taster		=33/67	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;