chr12-101486512-C-G

Variant names:

• chr12-101486512-C-G
• rs151030484
• NM_152323.3:c.488C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_152323.3(SPIC):​c.488C>G​(p.Thr163Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,613,986 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. T163I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00075 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (3 hom.)
• Consequence: SPIC NM_152323.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86
• Publications: 0 publications found

Genes affected

SPIC (HGNC:29549): (Spi-C transcription factor) The protein encoded by this gene regulates the development of red pulp macrophages, which are necessary for iron homeostasis and the recycling of red blood cells. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015591055).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152323.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIC	NM_152323.3	MANE Select	c.488C>G	p.Thr163Ser	missense	Exon 6 of 6	NP_689536.1	Q8N5J4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPIC	ENST00000551346.2	TSL:1 MANE Select	c.488C>G	p.Thr163Ser	missense	Exon 6 of 6	ENSP00000448580.1	Q8N5J4

Frequencies

GnomAD3 genomes AF: 0.000750 AC: 114 AN: 152096 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00128

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000966 AC: 243 AN: 251470 AF XY: 0.000876

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000693

Gnomad NFE exome AF: 0.00195

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.00106 AC: 1556 AN: 1461890 Hom.: 3 Cov.: 31 AF XY: 0.000983 AC XY: 715 AN XY: 727246

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.000449 AC: 24 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00132 AC: 1467 AN: 1112010

Other (OTH) AF: 0.000960 AC: 58 AN: 60396

GnomAD4 genome AF: 0.000750 AC: 114 AN: 152096 Hom.: 0 Cov.: 33 AF XY: 0.000633 AC XY: 47 AN XY: 74296

African (AFR) AF: 0.000169 AC: 7 AN: 41398

American (AMR) AF: 0.0000655 AC: 1 AN: 15258

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000472 AC: 5 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00128 AC: 87 AN: 68022

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.000750 Hom.: 0

Bravo AF: 0.000812

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.00132 AC: 160

EpiCase AF: 0.000872

EpiControl AF: 0.000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.82	L
PhyloP100		2.9
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.082
Sift	Benign	0.53	T
Sift4G	Benign	0.22	T
Polyphen		0.80	P
Vest4		0.20
MutPred		0.31		Gain of catalytic residue at R161 (P = 0.0197)
MVP		0.48
MPC		0.59
ClinPred		0.046	T
GERP RS		4.7
Varity_R		0.11
gMVP		0.11
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs151030484; hg19: chr12-101880290;