chr1-1217660-T-C

Variant names:

• chr1-1217660-T-C
• rs374737222
• NM_016176.6:c.920A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016176.6(SDF4):​c.920A>G​(p.Asn307Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: SDF4 NM_016176.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.21
• Publications: 0 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08829063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDF4	NM_016176.6	c.920A>G	p.Asn307Ser	missense_variant	Exon 7 of 7	ENST00000360001.12	NP_057260.3
SDF4	XM_047422111.1	c.941A>G	p.Asn314Ser	missense_variant	Exon 7 of 7		XP_047278067.1
SDF4	NM_016547.3	c.*10A>G		3_prime_UTR_variant	Exon 7 of 7		NP_057631.2
SDF4	XM_047422112.1	c.*10A>G		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.920A>G	p.Asn307Ser	missense_variant	Exon 7 of 7	1	NM_016176.6	ENSP00000353094.7

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152044 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 250214 AF XY: 0.0000369

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461622 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727100

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111946

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74406

African (AFR) AF: 0.0000963 AC: 4 AN: 41528

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67982

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000282 Hom.: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.941A>G (p.N314S) alteration is located in exon 7 (coding exon 6) of the SDF4 gene. This alteration results from a A to G substitution at nucleotide position 941, causing the asparagine (N) at amino acid position 314 to be replaced by a serine (S). 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	Benign	0.067
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.46	N
PhyloP100		3.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.087
Sift	Benign	0.21	T
Sift4G	Benign	0.21	T
Polyphen		0.0010	B
Vest4		0.13
MVP		0.10
MPC		0.29
ClinPred		0.12	T
GERP RS		3.0
Varity_R		0.038
gMVP		0.68
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs374737222; hg19: chr1-1153040;