chr1-1223336-T-A

Variant names:

• chr1-1223336-T-A
• NM_016176.6:c.464A>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016176.6(SDF4):​c.464A>T​(p.Tyr155Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. Y155C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SDF4 NM_016176.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.01

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.851

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDF4	NM_016176.6	c.464A>T	p.Tyr155Phe	missense_variant	Exon 4 of 7	ENST00000360001.12	NP_057260.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDF4	ENST00000360001.12	c.464A>T	p.Tyr155Phe	missense_variant	Exon 4 of 7	1	NM_016176.6	ENSP00000353094.7
SDF4	ENST00000263741.12	c.464A>T	p.Tyr155Phe	missense_variant	Exon 4 of 7	1		ENSP00000263741.8
SDF4	ENST00000403997.2	c.287A>T	p.Tyr96Phe	missense_variant	Exon 3 of 5	3		ENSP00000384207.2
SDF4	ENST00000465727.5	n.485A>T		non_coding_transcript_exon_variant	Exon 4 of 7	2		ENSP00000435962.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460774 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726684

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.71	D;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Benign	0.85	L;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Uncertain	0.58
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.043	D;D
Polyphen		0.95	P;D
Vest4		0.66
MutPred		0.64		Gain of catalytic residue at Y162 (P = 0.011);Gain of catalytic residue at Y162 (P = 0.011);
MVP		0.84
MPC		1.1
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.73
gMVP		0.58

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: chr1-1158716;