1-1218540-T-A

Position:

• chr1-1218540-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016176.6(SDF4):​c.809A>T​(p.Asn270Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SDF4 NM_016176.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.88

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]

SDF4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1943669).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDF4	NM_016176.6	c.809A>T	p.Asn270Ile	missense_variant	6/7	ENST00000360001.12	NP_057260.3
SDF4	NM_016547.3	c.809A>T	p.Asn270Ile	missense_variant	6/7		NP_057631.2
SDF4	XM_047422111.1	c.830A>T	p.Asn277Ile	missense_variant	6/7		XP_047278067.1
SDF4	XM_047422112.1	c.830A>T	p.Asn277Ile	missense_variant	6/7		XP_047278068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDF4	ENST00000360001.12	c.809A>T	p.Asn270Ile	missense_variant	6/7	1	NM_016176.6	ENSP00000353094.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Sep 25, 2024

The c.830A>T (p.N277I) alteration is located in exon 6 (coding exon 5) of the SDF4 gene. This alteration results from a A to T substitution at nucleotide position 830, causing the asparagine (N) at amino acid position 277 to be replaced by an isoleucine (I). 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	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Uncertain	0.54	D;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Benign	0.054
Sift	Benign	0.12	T;T
Sift4G	Uncertain	0.027	D;D
Polyphen		0.017	B;P
Vest4		0.40
MutPred		0.28		Loss of disorder (P = 0.0294);Loss of disorder (P = 0.0294);
MVP		0.32
MPC		0.50
ClinPred		0.62	D
GERP RS		0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.54

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: chr1-1153920;