1-1223943-T-C

Position:

• chr1-1223943-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_016176.6(SDF4):​c.331A>G​(p.Ile111Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: SDF4 NM_016176.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.59

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.

• PM1: In a binding_site (size 0) in uniprot entity CAB45_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20137215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDF4	NM_016176.6	c.331A>G	p.Ile111Val	missense_variant	3/7	ENST00000360001.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDF4	ENST00000360001.12	c.331A>G	p.Ile111Val	missense_variant	3/7	1	NM_016176.6	P1
SDF4	ENST00000263741.12	c.331A>G	p.Ile111Val	missense_variant	3/7	1
SDF4	ENST00000403997.2	c.157A>G	p.Ile53Val	missense_variant	2/5	3
SDF4	ENST00000465727.5	c.352A>G	p.Ile118Val	missense_variant, NMD_transcript_variant	3/7	2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.352A>G (p.I118V) alteration is located in exon 3 (coding exon 2) of the SDF4 gene. This alteration results from a A to G substitution at nucleotide position 352, causing the isoleucine (I) at amino acid position 118 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	Benign	0.15
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.26	T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.67	N;N
REVEL	Benign	0.21
Sift	Benign	0.23	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.0	B;B
Vest4		0.27
MutPred		0.39		Gain of methylation at K117 (P = 0.0585);Gain of methylation at K117 (P = 0.0585);
MVP		0.49
MPC		0.32
ClinPred		0.50	T
GERP RS		4.2
Varity_R		0.066
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr1-1159323;