1-1223352-C-T

Variant names:

• chr1-1223352-C-T
• NM_016176.6:c.448G>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PP3_Moderate

The NM_016176.6(SDF4):​c.448G>A​(p.Val150Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,455,900 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. V150L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SDF4 NM_016176.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.91

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity CAB45_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.86

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDF4	NM_016176.6	c.448G>A	p.Val150Met	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.448G>A	p.Val150Met	missense_variant	Exon 4 of 7	1	NM_016176.6	ENSP00000353094.7
SDF4	ENST00000263741.12	c.448G>A	p.Val150Met	missense_variant	Exon 4 of 7	1		ENSP00000263741.8
SDF4	ENST00000403997.2	c.271G>A	p.Val91Met	missense_variant	Exon 3 of 5	3		ENSP00000384207.2
SDF4	ENST00000465727.5	n.469G>A		non_coding_transcript_exon_variant	Exon 4 of 7	2		ENSP00000435962.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1455900 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 723966

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

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	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Pathogenic	0.30	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Pathogenic	0.81	D
MutationAssessor	Pathogenic	3.4	M;M
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.62
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		1.0	D;D
Vest4		0.85
MutPred		0.54		Loss of catalytic residue at V157 (P = 0.0258);Loss of catalytic residue at V157 (P = 0.0258);
MVP		0.94
MPC		1.1
ClinPred		0.92	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.31
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-1158732;